We lose ground: Global assessment of land subsidence impact extent.

Depletion of groundwater aquifers along with all of the associated quality and quantity problems which affect profitability of direct agricultural and urban users and linked groundwater-ecosystems have been recognized globally. During recent years, attention has been devoted to land subsidence-the loss of land elevation that occurs in areas with certain geological characteristics associated with aquifer exploitation. Despite the large socioeconomic impacts of land subsidence most of these effects are still not well analyzed and not properly recognized and quantified globally.

Thirty-day outcomes in frail older patients discharged home from the emergency department with acute heart failure: effects of high-risk criteria identified by the DEED FRAIL-AHF trial.

Objectives: To study the effect of high-risk criteria on 30-day outcomes in frail older patients with acute heart failure (AHF) discharged from an emergency department (ED) or an ED's observation and short-stay areas.

Material And Methods: Secondary analysis of discharge records in the Older AHF Key Data registry. We selected frail patients (aged > 70 years) discharged with AHF from EDs.

Phase I Trial of Cemiplimab, Radiotherapy, Cyclophosphamide, and Granulocyte Macrophage Colony-Stimulating Factor in Patients with Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma.

Lessons Learned: Cemiplimab in combination with radiation therapy, cyclophosphamide, and granulocyte macrophage colony-stimulating factor did not demonstrate efficacy above what can be achieved with other PD-1 inhibitor monotherapies in patients with refractory and metastatic head and neck squamous cell carcinoma. The safety profile of cemiplimab combination therapy was consistent with previously reported safety profiles of cemiplimab monotherapy. No new safety signal was observed.

Viral-Mediated Microbe Mortality Modulated by Ocean Acidification and Eutrophication: Consequences for the Carbon Fluxes Through the Microbial Food Web.

Anthropogenic carbon emissions are causing changes in seawater carbonate chemistry including a decline in the pH of the oceans. While its aftermath for calcifying microbes has been widely studied, the effect of ocean acidification (OA) on marine viruses and their microbial hosts is controversial, and even more in combination with another anthropogenic stressor, i.e.

A Predictive Score of Antitumour Activity of Novel Agents in Cancer Patients Treated in Early Phase Studies.

Introduction: Phase I trials aim to determine the maximum-tolerated dose of a particular drug while minimizing the number of patients exposed to either sub-therapeutic doses or severe toxicity. Thus, patient selection for phase I trials is a key component of any clinical trial design. Though several studies have been made to address this issue, patient selection still represents a major clinical challenge that needs further investigation.

Efficacy and safety of lurbinectedin and doxorubicin in relapsed small cell lung cancer. Results from an expansion cohort of a phase I study.

Background A phase I study found remarkable activity and manageable toxicity for doxorubicin (bolus) plus lurbinectedin (1-h intravenous [i.v.] infusion) on Day 1 every three weeks (q3wk) as second-line therapy in relapsed small cell lung cancer (SCLC).

Safety and activity of the TGFβ receptor I kinase inhibitor galunisertib plus the anti-PD-L1 antibody durvalumab in metastatic pancreatic cancer.

Background: We assessed the safety, efficacy, and pharmacokinetics of the transforming growth factor beta (TGFβ) receptor inhibitor galunisertib co-administered with the anti-programmed death-ligand 1 (PD-L1) antibody durvalumab in recurrent/refractory metastatic pancreatic cancer previously treated with ≤2 systemic regimens.

Methods: This was a two-part, single-arm, multinational, phase Ib study. In a dose-finding phase, escalating oral doses of galunisertib were co-administered on days 1-14 with fixed-dose intravenous durvalumab 1500 mg on day 1 every 4 weeks (Q4W), followed by an expansion cohort phase.

Incidence, clinical characteristics, risk factors and outcomes of meningoencephalitis in patients with COVID-19.

We investigated the incidence, clinical characteristics, risk factors, and outcome of meningoencephalitis (ME) in patients with COVID-19 attending emergency departments (ED), before hospitalization. We retrospectively reviewed all COVID patients diagnosed with ME in 61 Spanish EDs (20% of Spanish EDs, COVID-ME) during the COVID pandemic. We formed two control groups: non-COVID patients with ME (non-COVID-ME) and COVID patients without ME (COVID-non-ME).

Phase I dose-escalation study of NBTXR3 activated by intensity-modulated radiation therapy in elderly patients with locally advanced squamous cell carcinoma of the oral cavity or oropharynx.

Purpose: This phase I study assessed the safety of first-in-class radioenhancer nanoparticles, NBTXR3, in elderly or frail patients with locally advanced head and neck squamous cell carcinoma (HNSCC), ineligible for chemoradiation.

Methods: Patients with stage III or IVA (American Joint Committee on Cancer (AJCC) guidelines, 7th edition, 2010) HNSCC of the oral cavity or oropharynx, aged ≥70 or ≥65 years and ineligible to receive cisplatin, amenable to radiotherapy (RT) with curative intent, received NBTXR3 as a single intratumoural (IT) injection followed by activation by intensity-modulated radiation therapy (IMRT; 70 Gy). The NBTXR3 dose corresponded to a percentage of the baseline tumour volume, measured by magnetic resonance imaging.

Dosage of anti-PD-1 monoclonal antibodies: a cardinal open question.

Discovery and clinical development of monoclonal antibodies with the ability to interfere in the regulation of the immune response have significantly changed the landscape of oncology in recent years. Among the active agents licensed by the regulatory agencies, nivolumab and pembrolizumab are paradigmatic as the most relevant ones according to the magnitude of available data derived from the extensive preclinical and clinical experience. Although in both cases the respective data sheets indicate well-defined dosage regimens, a review of the literature permits to verify the existence of many issues still unresolved about dosing the two agents, so it must be considered an open question of potentially important consequences, in which to work to improve the effectiveness and efficiency of use.

Social and Individual Subjective Wellbeing and Capabilities in Chile.

The notion of social belongingness has been applied to different scales, from individual to social processes, and from subjective to objective dimensions. This article seeks to contribute to this multidimensional perspective on belongingness by drawing from the capabilities and subjective wellbeing perspectives. The specific aim is to analyze the relationships between capabilities-including those related to social belongingness-and individual and social subjective wellbeing.

Blocking TIM-3 in Treatment-refractory Advanced Solid Tumors: A Phase Ia/b Study of LY3321367 with or without an Anti-PD-L1 Antibody.

Purpose: T-cell immunoglobulin and mucin-domain-containing molecule-3 (TIM-3) blunts anticancer immunity and mediates resistance to programmed death 1 (PD-1) and PD ligand 1 (PD-L1) inhibitors. We assessed a novel, first-in-class, TIM-3 mAb, LY3321367, alone or in combination with the anti-PD-L1 antibody, LY300054 in patients with advanced solid tumor.

Patients And Methods: This open-label, multicenter, phase Ia/b study aimed to define the safety/tolerability and recommended phase II dose (RP2D) of LY3321367 with or without LY300054.

Evaluation and Management of Glenohumeral Instability With Associated Bone Loss: An Expert Consensus Statement Using the Modified Delphi Technique.

Purpose: To establish an international expert consensus, using the modified Delphi technique, on the evaluation and management of glenohumeral instability with associated bone loss.

Methods: A working group of 6 individuals generated a list of statements related to history and physical examination, imaging and specialized diagnostic tests, bone loss quantification and classification, treatment outcomes and complications, and rehabilitation for the management of glenohumeral instability associated with bone loss to form the basis of an initial survey for rating by a group of experts. The expert group (composed of 22 high-volume glenohumeral instability experts) was surveyed on 3 occasions to establish a consensus on the statements.

Aedes aegypti SGS1 is critical for Plasmodium gallinaceum infection of both the mosquito midgut and salivary glands.

Background: The invasion of the mosquito salivary glands by Plasmodium sporozoites is a critical step that defines the success of malaria transmission and a detailed understanding of the molecules responsible for salivary gland invasion could be leveraged towards control of vector-borne pathogens. Antibodies directed against the mosquito salivary gland protein SGS1 have been shown to reduce Plasmodium gallinaceum sporozoite invasion of Aedes aegypti salivary glands, but the specific role of this protein in sporozoite invasion and in other stages of the Plasmodium life cycle remains unknown.

Methods: RNA interference and CRISPR/Cas9 were used to evaluate the role of A.

Incidence, clinical, risk factors and outcomes of Guillain-Barré in Covid-19.

We diagnosed 11 Guillain-Barré syndrome (GBS) cases among 71,904 COVID patients attended at 61 Spanish emergency departments (EDs) during the 2-month pandemic peak. The relative frequency of GBS among ED patients was higher in COVID (0.15‰) than non-COVID (0.

The chaperonin CCT controls T cell receptor-driven 3D configuration of centrioles.

T lymphocyte activation requires the formation of immune synapses (IS) with antigen-presenting cells. The dynamics of membrane receptors, signaling scaffolds, microfilaments, and microtubules at the IS determine the potency of T cell activation and subsequent immune response. Here, we show that the cytosolic chaperonin CCT (chaperonin-containing TCP1) controls the changes in reciprocal orientation of the centrioles and polarization of the tubulin dynamics induced by T cell receptor in T lymphocytes forming an IS.

Cross-country differences in age trends in alcohol consumption among older adults: a cross-sectional study of individuals aged 50 years and older in 22 countries.

Background And Aims: Age-related changes in physiological, metabolic and medication profiles make alcohol consumption likely to be more harmful among older than younger adults. This study aimed to estimate cross-national variation in the quantity and patterns of drinking throughout older age, and to investigate country-level variables explaining cross-national variation in consumption for individuals aged 50 years and older.

Design: Cross-sectional observational study using previously harmonized survey data.

Voltage-dependent conformational changes of Kv1.3 channels activate cell proliferation.

The voltage-dependent potassium channel Kv1.3 has been implicated in proliferation in many cell types, based on the observation that Kv1.3 blockers inhibited proliferation.

Behavioural inhibition system sensitivity is no longer associated with psychotic-like experiences after controlling for depression and anxiety symptoms.

Aim: Elevated behavioural inhibition system sensitivity has been reported among schizophrenia patients. Yet, no study has investigated the relationship between behavioural inhibition system sensitivity and the occurrence of psychotic-like experiences (subthreshold psychotic symptoms considered to be less severe or impairing), despite evidence that behavioural inhibition system sensitivity is related to other forms of psychopathology known to co-occur with psychotic-like experiences, such as depression and anxiety. Thus, the aim of this study was to assess the relationship between behavioural inhibition system levels and psychotic-like experiences while controlling for depression and anxiety symptoms.

Comparison of radiological criteria for hyperprogressive disease in response to immunotherapy.

Hyperprogressive disease (HPD) is a concerning paradoxical acceleration of cancer growth induced by immune drugs. The lack of standard radiological criteria makes its study challenging. We reviewed the literature and compared the main criteria for HPD proposed by Ferté, Le Tourneau, Garralda and Caramella to address this relevant unmet need in Immune-oncology.

Why Does COVID-19 Affect Patients with Spinal Cord Injury Milder? A Case-Control Study: Results from Two Observational Cohorts.

The COVID-19 pandemic represents an unprecedented global challenge in this century. COVID-19 is a viral respiratory infection, yet the clinical characteristics of this infection differ in spinal cord injury patients from those observed in the general population. Cough and asthenia are the most frequent symptoms in this population.

T-cell-engaging Therapy for Solid Tumors.

T-cell engagers (TCE) are a rapidly evolving novel group of treatments that have in common the concurrent engagement of a T-cell surface molecule and a tumoral cell antigen. Bispecific antibodies and genetically engineered adoptive cell therapies, as chimeric antigen receptors or T-cell receptors, have similarities and differences among their mechanisms of action, toxicity profiles, and resistance pathways. Nevertheless, the success observed in the hematologic field has not been obtained with solid tumors yet, as they are biologically more complex and have few truly tumor-specific cell surface antigens that can be targeted with high avidity T cells.