Engineering the future of medicine: Natural products, synthetic biology and artificial intelligence for next-generation therapeutics.

The eXchange Unit between Thiolation domains approach and artificial intelligence (AI)-driven tools like Synthetic Intelligence are transforming nonribosomal peptide synthetase and polyketide synthase engineering, enabling the creation of novel bioactive compounds that address critical challenges like antibiotic resistance and cancer. These innovations expand chemical space and optimize biosynthetic pathways, offering precise and scalable therapeutic solutions. Collaboration across synthetic biology, AI, and clinical research is essential to translating these breakthroughs into next-generation treatments and revolutionizing drug discovery and patient care.

Implant irritation and removal rates in operatively treated multiple rib fractures: a 49-month follow-up study.

Purpose: Little is known about the prevalence, impact and change of the symptoms after implant removal due to irritation in multiple rib fractures. This study aims to explore these aspects to improve treatment decision-making.

Methods: Data was collected from two hospitals in the Netherlands and Switzerland.

Initial surgical management of spinal injuries in patients with multiple and/or severe injuries- the 2022 update of the German clinical practice guideline.

Purpose: Our aim was to update evidence-based and consensus-based recommendations for the initial surgical management of spinal (cord) injuries in patients with multiple and/or severe injuries based on current evidence. This guideline topic is part of the 2022 update of the German Guideline on the Treatment of Patients with Multiple and/or Severe Injuries.

Methods: MEDLINE and Embase were systematically searched to May 2021.

Transurethral resection of the prostate across continents: a meta-analysis evaluating quality of gold standard in the twenty-first century.

Purpose: To compare outcomes of transurethral resection of the prostate (TURP) across different regions worldwide over the past two decades.

Methods: A systematic review and meta-analysis of randomized clinical trials indexed to PubMed that assessed TURP. A total of 102 studies with 8,454 patients were included and grouped by continents: Europe, Asia, Africa, and Others (North America, South America, and Australia).

Pre-injury narcotic drug use in isolated severe traumatic brain injury: effect on outcomes.

Purpose: The aim of this study was to explore the association between pre-injury narcotic drug use (opioids, methadone, and/or oxycodone) and outcomes in isolated severe traumatic brain injury (TBI) patients.

Methods: ACS TQIP study included adult trauma patients (≥ 16 years) with complete drug and alcohol screening. Isolated severe TBI was defined as head trauma with AIS 3-5 and without significant extracranial trauma.

Functional genomics pipeline identifies CRL4 inhibition for the treatment of ovarian cancer.

Background: The goal of precision oncology is to find effective therapeutics for every patient. Through the inclusion of emerging therapeutics in a high-throughput drug screening platform, our functional genomics pipeline inverts the common paradigm to identify patient populations that are likely to benefit from novel therapeutic strategies.

Approach: Utilizing drug screening data across a panel of 46 cancer cell lines from 11 tumor lineages, we identified an ovarian cancer-specific sensitivity to the first-in-class CRL4 inhibitors KH-4-43 and 33-11.

Digoxin for reduction of circulating tumor cell cluster size in metastatic breast cancer: a proof-of-concept trial.

The presence of circulating tumor cell (CTC) clusters is associated with disease progression and reduced survival in a variety of cancer types. In breast cancer, preclinical studies showed that inhibitors of the Na/K ATPase suppress CTC clusters and block metastasis. Here we conducted a prospective, open-label, proof-of-concept study in women with metastatic breast cancer, where the primary objective was to determine whether treatment with the Na/K ATPase inhibitor digoxin could reduce mean CTC cluster size.

Cost and outcomes of side-to-side versus end-to-end anastomosis in right colectomy: a retrospective cohort study.

Background: The optimal anastomotic configuration for right-sided colectomies remains controversial, with comparable postoperative outcomes across techniques. Thus, economic considerations may play a larger role in decision-making within cost-constrained healthcare settings.

Methods: This retrospective cohort study evaluated right-sided colectomies with ileocolic anastomosis at a Swiss tertiary center between 2016 and 2021.

Biocementation beyond the Petri dish, scaling up to 900 L batches and a meter-scale column.

Microbial-induced calcite precipitation (MICP), which leverages ureolytic microorganisms, has received significant attention during the past decade as a promising method for sustainable building and geoenvironmental applications. However, transitioning from lab-scale experimentation to volumes suitable for practical use poses challenges. This study addresses these obstacles by screening and analyzing over 50 strains sourced from (i) a natural environment in the canton of Ticino in Switzerland; (ii) microorganism banks; and (iii) an industry-scale bioreactor.

Subsistence hunting impacts wildlife assemblages and functional ecology in tropical forests.

Unsustainable wild meat hunting poses a significant threat to wildlife and tropical forest ecosystems. While high levels of extraction linked to commercial trade have received significant attention, the sustainability of subsistence hunting by Indigenous Peoples in Africa has been less studied. Understanding how changing lifestyles, particularly the sedentarisation of former hunter-gatherers, have affected the use of forest resources is crucial for wildlife conservation and livelihoods.

Critical mobility in policy making for epidemic containment.

When considering airborne epidemic spreading in social systems, a natural connection arises between mobility and epidemic contacts. As individuals travel, possibilities to encounter new people either at the final destination or during the transportation process appear. Such contacts can lead to new contagion events.

Composite cardiac computed tomography angiography score for improved risk assessment in chronic coronary syndromes.

Agatston score, the degree of lumen narrowing categorized by CAD-RADS, high-risk atherosclerotic plaque features and pericoronary adipose tissue attenuation (PCAT) are parameters, which can be assessed non-invasively by coronary computed tomography angiography (CCTA) and aid risk stratification in patients with chronic coronary syndromes (CCS). However, few studies have so far compared the prognostic value of all those parameters together. To develop and test the prognostic value of a composite CCTA score, derived from Agatston score, CAD-RADS, high-risk plaques and PCAT in patients undergoing CCTA due to CCS.

The TLR7/9 adaptors TASL and TASL2 mediate IRF5-dependent antiviral responses and autoimmunity in mouse.

Endosomal nucleic acid sensing by Toll-like receptors (TLRs) is central to antimicrobial immunity and several autoimmune conditions such as systemic lupus erythematosus (SLE). The innate immune adaptor TASL mediates, via the interaction with SLC15A4, the activation of IRF5 downstream of human TLR7, TLR8 and TLR9, but the pathophysiological functions of this axis remain unexplored. Here we show that SLC15A4 deficiency results in a selective block of TLR7/9-induced IRF5 activation, while loss of TASL leads to a strong but incomplete impairment, which depends on the cell type and TLR engaged.

Zinc absorption from maize-based meals enriched with edible house crickets: a randomized crossover stable-isotope study in Kenyan pre-school children.

Edible insects have been proposed as a novel and sustainable source of protein and other essential nutrients for human consumption but nutrient absorption efficiency is still uncertain. We investigated zinc absorption from house crickets (Acheta domesticus) in a single-center and single-blinded cross-over study with children aged 24-36 months old in Kenya from September-November 2021. For this, children were randomized to consume two different experimental meals labeled with stable isotopes of zinc (Zn) at two different days, separated by a wash-out period of one month.

Aerobiology matters: Why people in the community access pollen information and how they use it.

Background: Globally, many pollen monitoring networks provide the community with daily pollen information, but there are limited data on health consumer uses and benefits. This research investigated why individuals in the community access pollen information, how they use it, and the perceived benefits.

Methods: In- and post-pollen season surveys (2017-2018 and 2018-2019) enquired about symptoms, diagnoses, symptom management, access, benefits and usefulness of pollen information provided by the AusPollen Partnership.

Best practices for including sex as a variable in appetite research.

Despite increasing recognition that sex is a critical variable in appetite research, many studies fail to include participants of both sexes, fail to consider reproductive physiology in participant selection, or include both sexes but fail to test for sex differences in outcomes. To help remedy this situation, this article seeks to engender enthusiasm for including sex as a variable in appetite research. We first illustrate some sex differences in healthy and disordered eating, including both male-female differences and differences across the menstrual cycle.

Association between frailty and specific comorbidities on oncological outcomes in metastatic hormone-sensitive and castration resistant prostate cancer.

Objective: Demographic changes will lead to higher proportions of metastatic hormone-sensitive (mHSPC) and castration resistant metastatic prostate cancer (mCRPC) patients with higher frailty index and multiple comorbidities.

Materials And Methods: We relied on an institutional tertiary-care database to explore the effect of frailty (Eastern Cooperative Oncology Group [ECOG]), as well as cardiovascular (CVD) and secondary malignancy (SecCa) comorbidities on overall survival (OS) and time to mCRPC in mHSPC and OS in mCRPC patients with Kaplan-Meyer estimates and Cox regression models.

Results: Of 802 mHSPC patients, 61% were ECOG0 vs.

Cytoreductive surgery in diffuse pleural mesothelioma. What have we learnt from MARS2, EORTC-L1205 and other recent studies?

Cytoreductive surgery remains controversial in pleural mesothelioma. The MARS2 trial suggested that extended pleurectomy decortication following neoadjuvant chemotherapy was associated with no survival benefit, more serious adverse events and poorer quality of life than systemic chemotherapy alone in patients with resectable pleural mesothelioma. However, patient selection, chemotherapy scheme, high surgical mortality (9 %) and poor outcomes in the surgical cohort have been raised by mesothelioma experts as potential issues in MARS2.

Respiratory impact of local anaesthetic volume after an interscalene brachial plexus block with an extrafascial injection: a randomised controlled double-blinded trial.

Background: We have previously demonstrated that an extrafascial injection of 20 ml of local anaesthetic for interscalene brachial plexus block (ISB) reduces the rate of hemidiaphragmatic paralysis by 70% compared with an intrafascial injection, with similar efficacy. In this double-blind trial, we tested the hypothesis that a local anaesthetic volume of 10 ml injected extrafascially would reduce the rate of hemidiaphragmatic paralysis vs a volume of 20 ml, while providing similar analgesia.

Methods: Sixty ASA physical status 1-3 patients scheduled for elective shoulder surgery under general anaesthesia were randomised to receive ultrasound-guided extrafascial ISB using ropivacaine 0.

A step towards understanding plastic complexity: Antimony speciation in consumer plastics and synthetic textiles revealed by XAS.

We identified the antimony species present in a wide variety of plastic samples by X ray absorption spectroscopy (XAS) at the Sb L-edge. The samples contained different concentrations of antimony (Sb), ranging from PET bottles in which Sb compounds are used as catalysts, with concentrations around 300 mg/kg, to electrical equipment in which the element is used as a flame retardant, with concentrations of several tens of thousands of mg/kg. Although the shape of the spectra at the L-edge is quite similar for all Sb reference materials, we were able to identify antimony glycolate or acetate in PET bottles, bound organic Sb in c-PET trays and senarmontite in electrical materials as the main Sb components.

Forensic analysis of an alleged improvised explosive device (IED) from a multidisciplinary perspective: Organisation and outcomes of the ENFSI 2023 exercise.

Interdisciplinary examination of test materials requires careful consideration of how forensic routines can influence each other. This influence can be direct and obvious, or indirect and subtle. A multidisciplinary collaborative exercise (MdCE) should test a forensic laboratory's ability to account for these difficulties.

International benchmarking of stage at diagnosis for six childhood solid tumours (the BENCHISTA project): a population-based, retrospective cohort study.

Background: International variation in childhood cancer survival might be explained by differences in stage at diagnosis, among other factors. As part of the BENCHISTA project, we aimed to assess geographical variation in tumour stage at diagnosis through the application, by population-based cancer registries working with clinicians, of the international consensus Toronto Childhood Cancer Stage Guidelines.

Methods: This population-based, retrospective cohort study involved 67 cancer registries from 23 European countries, Australia, Brazil, Japan, and Canada.