Subjective and Objective Assessment of the Preferred Rotational Cervical Spine Position in Infants with an Upper Cervical Spine Dysfunction: A Cross-Sectional Study.

Background: We aimed to assess (1) the awareness of parents regarding the cervical rotation preference of their infant and the agreement of the parent, clinician and objective assessments, and (2) the test-retest reliability for objective (measured) rotation, lateral flexion and combined flexion-rotation.

Methods: This was a cross-sectional study including 69 infants aged three to six months with upper cervical spine dysfunction, without general health issues or specific cervical spine impairments. No treatment was applied.

CD70 CAR T cells secreting an anti-CD33/anti-CD3 dual targeting antibody overcome antigen heterogeneity in AML.

CD70 has emerged as a promising target in acute myeloid leukemia (AML), and we have previously demonstrated the potency of an optimized CD70-targeted ligand-based CAR. However, here, we identify in vivo CD70 antigen escape as a limitation of single antigen targeting. Combination targeting of CD70 and CD33 may overcome AML antigen heterogeneity.

A Dirt(y) World in a Changing Climate: Importance of Heat Stress in the Risk Assessment of Pesticides for Soil Arthropods.

The rise in global temperatures and increasing severity of heat waves pose significant threats to soil organisms, disrupting ecological balances in soil communities. Additionally, the implications of environmental pollution are exacerbated in a warmer world, as changes in temperature affect the uptake, transformation and elimination of toxicants, thereby increasing the vulnerability of organisms. Nevertheless, our understanding of such processes remains largely unexplored.

Acclimation temperature influences the thermal sensitivity of injury accumulation in at extreme low and high temperatures.

The importance of thermal acclimation for the Thermal Death Time (TDT) landscape of the common soil living springtail, (Collembola, Isotomidae), was investigated. To this aim, we acclimated adult springtails at 10 °C (cold-acclimation) and 20 °C (warm-acclimation), respectively. In static thermal tolerance assays, we found the relationship between survival and exposure time at a number of stressful high and low temperatures.

Comparative analysis of Bcl-2 family protein overexpression in CAR T cells alone and in combination with BH3 mimetics.

Approximately 50% of patients with hematologic malignancies relapse after chimeric antigen receptor (CAR) T cell treatment; mechanisms of failure include loss of CAR T persistence and tumor resistance to apoptosis. We hypothesized that both of these challenges could potentially be overcome by overexpressing one or more of the Bcl-2 family proteins in CAR T cells to reduce their susceptibility to apoptosis, both alone and in the presence of BH3 mimetics, which can be used to activate apoptotic machinery in malignant cells. We comprehensively investigated overexpression of different Bcl-2 family proteins in CAR T cells with different signaling domains as well as in different tumor types.

Phase 1 study of CAR-37 T cells in patients with relapsed or refractory CD37+ lymphoid malignancies.

We report a first-in-human clinical trial using chimeric antigen receptor (CAR) T cells targeting CD37, an antigen highly expressed in B- and T-cell malignancies. Five patients with relapsed or refractory CD37+ lymphoid malignancies were enrolled and infused with autologous CAR-37 T cells. CAR-37 T cells expanded in the peripheral blood of all patients and, at peak, comprised >94% of the total lymphocytes in 4 of 5 patients.

Complete genome sequence of the linezolid-resistant clinical N23-3408 linked to a livestock lineage in Switzerland.

Here, we report the complete genome of human clinical linezolid-resistant N23-3408. N23-3408 harbored a 59.5 kb plasmid with antimicrobial resistance genes , (B), , , (L), and (M).

Mesothelin CAR T Cells Secreting Anti-FAP/Anti-CD3 Molecules Efficiently Target Pancreatic Adenocarcinoma and its Stroma.

Purpose: Targeting solid tumors with chimeric antigen receptor (CAR) T cells remains challenging due to heterogenous target antigen expression, antigen escape, and the immunosuppressive tumor microenvironment (TME). Pancreatic cancer is characterized by a thick stroma generated by cancer-associated fibroblasts (CAF), which may contribute to the limited efficacy of mesothelin-directed CAR T cells in early-phase clinical trials. To provide a more favorable TME for CAR T cells to target pancreatic ductal adenocarcinoma (PDAC), we generated T cells with an antimesothelin CAR and a secreted T-cell-engaging molecule (TEAM) that targets CAF through fibroblast activation protein (FAP) and engages T cells through CD3 (termed mesoFAP CAR-TEAM cells).

Functional and Radiologic Outcomes of Degenerative Versus Traumatic Full-Thickness Rotator Cuff Tears Involving the Supraspinatus Tendon.

Background: Arthroscopic rotator cuff repair (ARCR) is among the most commonly performed orthopaedic procedures. Several factors-including age, sex, and tear severity-have been identified as predictors for outcome after repair. The influence of the tear etiology on functional and structural outcome remains controversial.

Concordance of shoulder strength assessments using a spring balance and isometric dynamometer in patients before and after arthroscopic rotator cuff repair.

Background: Shoulder strength is an essential assessment to monitor the outcome of treatment interventions. Isometric strength assessment in the Constant Score (CS) was initially measured with a cable tensiometer or spring balance (SB). Some authors have questioned the validity of this strength assessment and the resulting CS.

"Hurdles race for CAR T-cell therapy in digestive tract cancer".

Digestive tract cancers (DTC) belong to the most investigated family of tumors. The incidence, prevalence, and mortality rate of DTC remain high, especially for patients with pancreatic cancer. Even though immunotherapy such as immune checkpoint inhibitors (ICI) have revolutionized the treatment of solid cancer types, ICI are still restricted to a very small group of patients and seem to be more efficacious in combination with chemotherapy.

Thermomechanical Stress Analysis of Hydrated Vital Gluten with Large Amplitude Oscillatory Shear Rheology.

Vital gluten is increasingly researched as a non-food product for biodegradable materials. During processing, the protein network is confronted with increased thermal and mechanical stress, altering the network characteristics. With the prospect of using the protein for materials beyond food, it is important to understand the mechanical properties at various processing temperatures.

Surgical Outcomes, Long-Term Recurrence Rate, and Resource Utilization in a Prospective Cohort of 165 Patients Treated by Transanal Total Mesorectal Excision for Distal Rectal Cancer.

A transanal total mesorectal excision (taTME) is a smart alternative to a conventional TME. However, worrisome reports of a high recurrence and complications triggered a moratorium in a few countries. This study assessed the outcomes and resource utilization of a taTME.

Evaluation of the physiological benefits of a passive back-support exoskeleton during lifting and working in forward leaning postures.

Musculoskeletal disorders affecting the back are highly prevalent in fields of occupation involving repetitive lifting and working in forward leaning postures. Back-support exoskeletons are developed to relieve workers in physically demanding occupations. This study investigates the physiological effects of a lightweight exoskeleton which provides support through textile springs worn on the back.

Subpectoral biceps tenodesis with BicepsButton fixation in the young population: which technique works best?

Background: Injuries of the long head of the biceps (LHB) tendon are a prevalent source of anterior shoulder pain and are commonly treated with tenodesis. Not only a stable fixation of the LHB but also anatomic restoration of the length-tension relationship plays a central role in providing satisfactory functional and cosmetic outcomes, especially in young patients. We report the clinical outcomes of 2 different subpectoral tenodesis techniques using unicortical button fixation.

Correlation between the level of evidence and the class of recommendations concerning the pharmacological aspects of the Guidelines of the European Society of Cardiology.

Background The reliability of the recommendations affecting the clinical decisions is being continuously weighed in everyday practice (Gershlick, 2018). The objective of our study was to assess the consistency of the evidence behind the recommendations. Methods We narrowed our focus on the pharmacotherapeutic aspects of the most recent 38 European Society of Cardiology guidelines and analyzed the correlation between the level of evidence (LoE) classified as A, B and C and the class of recommendations (CoR) subdivided into I, IIa, IIb and III.

Non-cleavable hinge enhances avidity and expansion of CAR-T cells for acute myeloid leukemia.

Chimeric antigen receptor (CAR) T cell therapy is effective in lymphoid malignancies, but there has been limited data in myeloid cancers. Here, we start with a CD27-based CAR to target CD70 ("native") in acute myeloid leukemia (AML), and we find modest efficacy in vivo, consistent with prior reports. We then use orthogonal approaches to increase binding on both the tumor and CAR-T cell sides of the immune synapse: a pharmacologic approach (azacitidine) to increase antigen density of CD70 in myeloid tumors, and an engineering approach to stabilize binding of the CAR to CD70.

Blockade or Deletion of IFNγ Reduces Macrophage Activation without Compromising CAR T-cell Function in Hematologic Malignancies.

Unlabelled: Chimeric antigen receptor (CAR) T cells induce impressive responses in patients with hematologic malignancies but can also trigger cytokine release syndrome (CRS), a systemic toxicity caused by activated CAR T cells and innate immune cells. Although IFNγ production serves as a potency assay for CAR T cells, its biologic role in conferring responses in hematologic malignancies is not established. Here we show that pharmacologic blockade or genetic knockout of IFNγ reduced immune checkpoint protein expression with no detrimental effect on antitumor efficacy against hematologic malignancies in vitro or in vivo.

Single-center experience using anakinra for steroid-refractory immune effector cell-associated neurotoxicity syndrome (ICANS).

In addition to remarkable antitumor activity, chimeric antigen receptor (CAR) T-cell therapy is associated with acute toxicities such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Current treatment guidelines for CRS and ICANS include use of tocilizumab, a monoclonal antibody that blocks the interleukin (IL)-6 receptor, and corticosteroids. In patients with refractory CRS, use of several other agents as third-line therapy (including siltuximab, ruxolitinib, anakinra, dasatinib, and cyclophosphamide) has been reported on an anecdotal basis.

Parental experience of the neuromotor development of children with congenital heart disease: an exploratory qualitative study.

Background: Children with severe congenital heart disease (CHD) are a group of children at risk for neurodevelopmental impairments. Motor development is the first domain to show a delay during the first year of life and may significantly contribute to parental concerns, stress, and difficulties in early child-parent attachment. Thus, the aim of the study was to better understand the wishes and concerns of parents of children with CHD and explore their experience of their children's neuromotor development in the first year of life.

New CARs on and off the road: challenges and new developments in CAR-T cell therapy.

Building on the tremendous success of chimeric antigen receptor T-cell therapy in hematological malignancies, there are efforts under way to overcome the challenges associated with this treatment and expand its application to solid tumors. In this fast-evolving field, new therapeutic options are constantly generated, tested in model systems, and further evaluated in clinical trials. In this review, we provide an overview of recent challenges and developments associated with engineered T cells and chimeric antigen receptor T-cell applications.

Haplotype structure defines effects of common DPYD variants c.85T > C (rs1801265) and c.496A > G (rs2297595) on dihydropyrimidine dehydrogenase activity: Implication for 5-fluorouracil toxicity.

Aims: The aim of this study was to identify risk variants and haplotypes that impair dihydropyrimidine dehydrogenase (DPD) activity and are, therefore, candidate risk variants for severe toxicity to 5-fluorouracil (5-FU) chemotherapy.

Methods: Plasma dihydrouracil/uracil (UH /U) ratios were measured as a population marker for DPD activity in a total of 1382 subjects from 4 independent studies. Genotype and haplotype correlations with UH /U ratios were assessed.

Thermally induced gluten modification observed with rheology and spectroscopies.

The protein vital gluten is mainly used for food while interest for non-food applications, like biodegradable materials, increases. In general, the structure and functionality of proteins is highly dependent on thermal treatments during production or modification. This study presents conformational changes and corresponding rheological effects of vital wheat gluten depending on temperature.

IgA Triggers Cell Death of Neutrophils When Primed by Inflammatory Mediators.

IVIG preparations consisting of pooled IgG are increasingly used for the treatment of autoimmune diseases. IVIG is known to regulate the viability of immune cells, including neutrophils. We report that plasma-derived IgA efficiently triggers death of neutrophils primed by cytokines or TLR agonists.