Unequal distributions of crowdsourced weather data in England and Wales.

Personal weather stations (PWS) can provide useful data on urban climates by densifying the number of weather measurements across major cities. They do so at a lower cost than official weather stations by national meteorological services. Despite the increasing use of PWS data, little attention has yet been paid to the underlying socio-economic and environmental inequalities in PWS coverage. Using social deprivation, demographic, and environmental indicators in England and Wales, we characterize existing inequalities in the current coverage of PWS. We find that there are fewer PWS in more deprived areas which also observe higher proportions of ethnic minorities, lower vegetation coverage, higher building height and building surface fraction, and lower proportions of inhabitants under 65 years old. This implies that data on urban climate may be less reliable or more uncertain in particular areas, which may limit the potential for climate adaptation and empowerment in those communities.

The tuning of tuning: How adaptation influences single cell information transfer.

Sensory neurons reconstruct the world from action potentials (spikes) impinging on them. To effectively transfer information about the stimulus to the next processing level, a neuron needs to be able to adapt its working range to the properties of the stimulus. Here, we focus on the intrinsic neural properties that influence information transfer in cortical neurons and how tightly their properties need to be tuned to the stimulus statistics for them to be effective. We start by measuring the intrinsic information encoding properties of putative excitatory and inhibitory neurons in L2/3 of the mouse barrel cortex. Excitatory neurons show high thresholds and strong adaptation, making them fire sparsely and resulting in a strong compression of information, whereas inhibitory neurons that favour fast spiking transfer more information. Next, we turn to computational modelling and ask how two properties influence information transfer: 1) spike-frequency adaptation and 2) the shape of the IV-curve. We find that a subthreshold (but not threshold) adaptation, the 'h-current', and a properly tuned leak conductance can increase the information transfer of a neuron, whereas threshold adaptation can increase its working range. Finally, we verify the effect of the IV-curve slope in our experimental recordings and show that excitatory neurons form a more heterogeneous population than inhibitory neurons. These relationships between intrinsic neural features and neural coding that had not been quantified before will aid computational, theoretical and systems neuroscientists in understanding how neuronal populations can alter their coding properties, such as through the impact of neuromodulators. Why the variability of intrinsic properties of excitatory neurons is larger than that of inhibitory ones is an exciting question, for which future research is needed.

Noble Gas Analyses to Distinguish Between Surface and Subsurface Brine Releases at a Legacy Oil Site.

Attributing the sources of legacy contamination, including brines, is important to determine remediation options and to allocate responsibility. To make sound remediation decisions, it is necessary to distinguish subsurface sources, such as leaking oil and gas ("O&G") wells or natural upward fluid migrations, from surface releases. While chemical signatures of surface and subsurface releases may be similar, they are expected to imprint specific dissolved noble gas signatures, caused by the accumulation of terrigenic noble gases in subsurface leaks or re-equilibration of noble gases following surface releases. We demonstrate that only a historic surface release influenced the dissolved noble gas signature of groundwater in monitoring wells contaminated with brine near an abandoned O&G well, rather than subsurface leakage from the well. Elevated brine concentrations were associated with lower terrigenic helium concentrations, indicating re-equilibration with atmospheric helium at the surface during the release. Geophysical surveying indicating elevated salinity in surficial soils upgradient of the wells further supported the interpretation of the noble gas data. Eliminating the possibility that subsurface leakage was the source of the plume was critical to selecting the proper remedial action at the site, which otherwise may have included an unnecessary and costly well re-abandonment. This study demonstrates the use of noble gas analysis to compare potential sources of brine contamination in groundwater and to exclude subsurface leakage as a potential source in an oilfield.

Decentralising DOT for drug-susceptible TB from the health facilities to the community level in Togo.

In Togo, the COVID-19 pandemic paved the way for decentralising directly observed treatment (DOT) to the community level through the evaluation of two innovative community-based DOT approaches-a community health worker-based (CHW-DOT) and family-based (FB-DOT). METHODS We conducted an observational prospective study from April 2021 to January 2022. Sputum conversion at Month 2 and favourable treatment outcomes at Month 6 were assessed and compared between the two groups. Sociodemographic and clinical factors related to these outcomes were identified. RESULTS A total of 182 TB patients were enrolled. The CHW-DOT group had significantly increased odds of sputum conversion (aOR 2.95, 95% CI 1.09-7.98) and lower odds of unsuccessful treatment outcomes (aOR 0.37, 95% CI 0.13-1.1). Non-smokers had 4.85 higher odds of converting than smokers (aOR 4.85, 95% CI 1.76-13.42) and lower odds of an unsuccessful treatment than smokers (aOR 0.11, 95% CI 0.04-0.32). CONCLUSION CHW-DOT is associated with higher sputum smear conversion rates and a more favourable treatment outcome. The use of tobacco, significantly associated with outcomes, also suggests that a smoking cessation component may be a valuable adjunct to a CHW-DOT approach during TB treatment..

Opportunities for risk-taking during play alters cognitive performance and prefrontal inhibitory signalling in rats of both sexes.

Social play behaviour is a rewarding activity that can entail risks, thus allowing young individuals to test the limits of their capacities and to train their cognitive and emotional adaptability to challenges. Here, we tested in rats how opportunities for risk-taking during play affect the development of cognitive and emotional capacities and medial prefrontal cortex (mPFC) function, a brain structure important for risk-based decision making. Male and female rats were housed socially or social play-deprived (SPD) between postnatal day (P)21 and P42. During this period, half of both groups were daily exposed to a high-risk play environment. Around P85, all rats were tested for cognitive performance and emotional behaviour after which inhibitory currents were recorded in layer 5 pyramidal neurons in mPFC slices. We show that playing in a high-risk environment altered cognitive flexibility in both sexes and improved behavioural inhibition in males. High-risk play altered anxiety-like behaviour in the elevated plus maze in males and in the open field in females, respectively. SPD affected cognitive flexibility in both sexes and decreased anxiety-like behaviour in the elevated plus maze in females. We found that synaptic inhibitory currents in the mPFC were increased in male, but not female, rats after high-risk play, while SPD lowered prefrontal cortex (PFC) synaptic inhibition in both sexes. Together, our data show that exposure to risks during play affects the development of cognition, emotional behaviour and inhibition in the mPFC. Furthermore, our study suggests that the opportunity to take risks during play cannot substitute for social play behaviour.

Update on the Sentinel Node Procedure in Vulvar Cancer.

Early-stage vulvar cancer is managed by a local excision of the primary tumor and, if indicated, a sentinel node (SN) biopsy to assess the need for further groin treatment. With the SN procedure, many patients can be treated less radically and will experience less complications and morbidity compared with an inguinofemoral lymphadenectomy (IFL). Still, the SN procedure can be further optimized. Different tracers for detecting the SN are being investigated, aiming to optimize detection rates and decrease the burden of the procedure and short-term complications. Until now, no standardized protocols exist for the pathologic workup of the SN, possibly leading to discrepancies in detection of metastases between institutes using different methods. New techniques, such as one-step nucleic amplification, seem to have potential in accurately detecting metastases in other cancers, but have not yet been investigated in vulvar squamous cell carcinoma (VSCC). Furthermore, several studies have investigated the possibility to broaden the indications for the SN procedure, such as its use in recurrent disease, larger tumors, or multifocal tumors. Although these studies show encouraging results, cohorts are small and further studies are needed. Prospective studies are currently investigating these subgroups. Lastly, several studies investigated optimization of groin treatment of patients with a metastatic SN. Inguinofemoral radiotherapy is a good alternative to IFL in patients with micrometastases in the SN, with comparable efficacy and less treatment-related morbidity. Reduction of the radicality of groin treatment is also possible in other ways, such as omitting contralateral IFL in patients with lateralized tumors and a unilateral metastatic SN. In conclusion, the SN procedure is an established procedure in early-stage VSCC, although optimization of the technique, pathologic workup, indications, and treatment in the setting of metastatic disease are the subject of ongoing research.

Early radiologic and metabolic tumour response assessment during combined chemo-radiotherapy for locally advanced NSCLC.

Background: The role of early treatment response for patients with locally advanced non-small cell lung cancer (LA-NSCLC) treated with concurrent chemo-radiotherapy (cCRT) is unclear. The study aims to investigate the predictive value of response to induction chemotherapy (iCX) and the correlation with pattern of failure (PoF). Materials and methods: Patients with LA-NSCLC treated with cCRT were included for analyses (n = 276). Target delineations were registered from radiotherapy planning PET/CT to diagnostic PET/CT, in between which patients received iCX. Volume, sphericity, and SUVpeak were extracted from each scan. First site of failure was categorised as loco-regional (LR), distant (DM), or simultaneous LR+M (LR+M). Fine and Gray models for PoF were performed: a baseline model (including performance status (PS), stage, and histology), an image model for squamous cell carcinoma (SCC), and an image model for non-SCC. Parameters included PS, volume (VOL) of tumour, VOL of lymph nodes, ΔVOL, sphericity, SUVpeak, ΔSUVpeak, and oligometastatic disease. Results: Median follow-up was 7.6 years. SCC had higher sub-distribution hazard ratio (sHR) for LRF (sHR = 2.771 [1.577:4.87], p < 0.01) and decreased sHR for DM (sHR = 0.247 [0.125:0.485], p  <  0.01). For both image models, high diagnostic SUVpeak increased risk of LRF (sHR = 1.059 [1.05:1.106], p < 0.01 for SCC, sHR = 1.12 [1.03:1.21], p < 0.01 for non-SCC). Patients with SCC and less decrease in VOL had higher sHR for DM (sHR = 1.025[1.001:1.048] pr. % increase, p = 0.038). Conclusion: Poor response in disease volume was correlated with higher sHR of DM for SCC, no other clear correlation of response and PoF was observed. Histology significantly correlated with PoF with SCC prone to LRF and non-SCC prone to DM as first site of failure. High SUVpeak at diagnosis increased the risk of LRF for both histologies.

Etiology and perinatal outcomes between early and late-onset nonimmune hydrops fetalis

SUMMARY OBJECTIVE: We aimed to compare the etiology and perinatal outcomes of non-immune hydrops fetalis diagnosed early- and late-onset at our hospital. METHODS: The records of the patients who applied to our department were reviewed, and we reached 42 non-immune hydrops fetalis cases retrospectively and examined the medical records. Hydrops diagnosis week, birth week, accompanying anomalies, and perinatal outcomes were compared as ≤12 weeks (early-onset) and >12 weeks (late-onset). RESULTS: The prevalence of non-immune hydrops fetalis was 0.05%, and the median week of diagnosis for hydrops was 18 weeks. Consanguinity (16.7%) was found in seven pregnancies, and the other seven patients (16.7%) had a history of hydrops in previous pregnancies. Anomalies of the skeletal system, central nervous system, and gastrointestinal tract accounted for 66.7% of ≤12 weeks in non-immune hydrops fetalis cases. Cardiac abnormalities were more common (26.7%) in patients at > 12 weeks (p=0.078). A statistically significant difference was found between the distribution of week of birth and week of diagnosis (p=0.029). Notably, 66.7% of patients diagnosed before week 12 and 23.3% of patients diagnosed after week 12 delivered their babies before week 24. Spontaneous intrauterine death occurred before week 12 in 45.5% (n=5) of non-immune hydrops fetalis and after week 12 in 39.1% (n=9) of non-immune hydrops fetalis. Notably, 69.2% (n=9) of the patients who had prenatal invasive testing resulted in normal karyotype. CONCLUSION: In this study, most of the fetuses diagnosed with early-onset non-immune hydrops fetalis were born in the first 24 weeks. Additionally, live birth rates and cardiac anomalies were observed to be higher in late-onset non-immune hydrops fetalis.

Valor pronóstico de los parámetros metabólicos volumétricos del tumor primario y ganglios linfáticos en el PET/TC pretratamiento en el carcinoma nasofaríngeo / Prognostic value of primary tumor and lymph node volumetric metabolic parameters at pre-treatment F-18 FDG PET/CT in nasopharyngeal carcinoma

Objetivo El objetivo de este estudio fue evaluar el significado pronóstico de los parámetros metabólicos volumétricos de la PET/TC pretratamiento junto con las características clínicas en pacientes con carcinoma nasofaríngeo no metastásico. Material y métodos Setenta y nueve pacientes con carcinoma nasofaríngeo se sometieron a una PET/TC con [18F]FDG para evaluación previa al tratamiento y se incluyeron en este estudio. Se analizaron las características del paciente (edad, histopatología del tumor, estadio T/N, tamaño del tumor primario y ganglio cervical más grande) y parámetros PET: valores de captación estandarizados máximo, medio y pico (SUVmáx, SUVmean, SUVpico), volumen tumoral metabólico (MTV) y glucólisis de lesión total (TLG) para el tumor primario y el ganglio linfático cervical más grande. El análisis de supervivencia para la supervivencia libre de progresión (PFS) y la supervivencia global (OS) se realizó con el método de Kaplan-Meier utilizando los hallazgos de PET y las características clínicas. Resultados La mediana de duración del seguimiento fue de 29,7 meses (rango 3-125 meses). El MTV del tumor primario y el MTV de los ganglios linfáticos cervicales fueron factores pronósticos independientes para la PFS (p = 0,025 y p = 0,004, respectivamente). Los pacientes con MTV del tumor primario > 19,4 y los pacientes con MTV de los ganglios linfáticos > 3,4 tuvieron una PFS más corta. Para OS, la edad y el tamaño del ganglio linfático fueron factores pronósticos independientes (p = 0,031 y p = 0,029). Los pacientes mayores de 54 años y los pacientes con ganglios linfáticos > 1 cm se asociaron con una OS disminuida. Conclusión El MTV del tumor primario y el MTV de los ganglios linfáticos en la PET/TC previa al tratamiento son factores pronósticos significativos para la PFS a largo plazo en el carcinoma nasofaríngeo no metastásico (AU)

Background The aim of this study was to evaluate the prognostic significance of volumetric metabolic parameters of pre-treatment PET/CT along with clinical characteristics in patients with non-metastatic nasopharyngeal carcinoma. Material and methods Seventy-nine patients with nasopharyngeal carcinoma underwent F18-FDG PET/CT for pretreatment evaluation and included in this study. The patient features (patient age, tumor histopathology, T and N stage, size of primary tumor and the largest cervical lymph node) and PET parameters were analyzed: maximum, mean and peak standardized uptake values (SUVmax, SUVmean, SUVpeak), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) for primary tumor and largest cervical lymph node. After treatment, patients were evaluated for disease progression and mortality. Survival analysis for progression-free survival (PFS) and over-all survival (OS) was performed with Kaplan–Meier method using PET findings and clinical characteristics. Results The median follow-up duration was 29.7 months (range 3–125 months). Among clinical characteristics, no parameters had significance association for PFS. Primary tumor-MTV and cervical lymphnode-MTV were independent prognostic factors for PFS (p = 0.025 and p = 0.004, respectively). Patients with primary tumor-MTV > 19.4 and patients with lymph node-MTV > 3.4 had shorter PFS. For OS, age and the size of the lymph node were independent prognostic factor (p = 0.031 and p = 0.029). Patients with age over 54 years and patients with lymph node size > 1 cm were associated with decreased OS. Conclusion Primary tumor-MTV and lymph node-MTV on pre-treatment PET/CT are significant prognostic factors for long-term PFS in non-metastatic nasopharyngeal carcinoma (AU)

The undiscovered biosynthetic potential of the Greenland Ice Sheet microbiome.

The Greenland Ice Sheet is a biome which is mainly microbially driven. Several different niches can be found within the glacial biome for those microbes able to withstand the harsh conditions, e.g., low temperatures, low nutrient conditions, high UV radiation in summer, and contrasting long and dark winters. Eukaryotic algae can form blooms during the summer on the ice surface, interacting with communities of bacteria, fungi, and viruses. Cryoconite holes and snow are also habitats with their own microbial community. Nevertheless, the microbiome of supraglacial habitats remains poorly studied, leading to a lack of representative genomes from these environments. Under-investigated extremophiles, like those living on the Greenland Ice Sheet, may provide an untapped reservoir of chemical diversity that is yet to be discovered. In this study, an inventory of the biosynthetic potential of these organisms is made, through cataloging the presence of biosynthetic gene clusters in their genomes. There were 133 high-quality metagenome-assembled genomes (MAGs) and 28 whole genomes of bacteria obtained from samples of the ice sheet surface, cryoconite, biofilm, and snow using culturing-dependent and -independent approaches. AntiSMASH and BiG-SCAPE were used to mine these genomes and subsequently analyze the resulting predicted gene clusters. Extensive sets of predicted Biosynthetic Gene Clusters (BGCs) were collected from the genome collection, with limited overlap between isolates and MAGs. Additionally, little overlap was found in the biosynthetic potential among different environments, suggesting specialization of organisms in specific habitats. The median number of BGCs per genome was significantly higher for the isolates compared to the MAGs. The most talented producers were found among Proteobacteria. We found evidence for the capacity of these microbes to produce antimicrobials, carotenoid pigments, siderophores, and osmoprotectants, indicating potential survival mechanisms to cope with extreme conditions. The majority of identified BGCs, including those in the most prevalent gene cluster families, have unknown functions, presenting a substantial potential for bioprospecting. This study underscores the diverse biosynthetic potential in Greenland Ice Sheet genomes, revealing insights into survival strategies and highlighting the need for further exploration and characterization of these untapped resources.

Exploring microbial diversity in Greenland Ice Sheet supraglacial habitats through culturing-dependent and -independent approaches.

The microbiome of Greenland Ice Sheet supraglacial habitats is still underinvestigated, and as a result there is a lack of representative genomes from these environments. In this study, we investigated the supraglacial microbiome through a combination of culturing-dependent and -independent approaches. We explored ice, cryoconite, biofilm, and snow biodiversity to answer: (1) how microbial diversity differs between supraglacial habitats, (2) if obtained bacterial genomes reflect dominant community members, and (3) how culturing versus high throughput sequencing changes our observations of microbial diversity in supraglacial habitats. Genomes acquired through metagenomic sequencing (133 high-quality MAGs) and whole genome sequencing (73 bacterial isolates) were compared to the metagenome assemblies to investigate abundance within the total environmental DNA. Isolates obtained in this study were not dominant taxa in the habitat they were sampled from, in contrast to the obtained MAGs. We demonstrate here the advantages of using metagenome SSU rRNA genes to reflect whole-community diversity. Additionally, we demonstrate a proof-of-concept of the application of in situ culturing in a supraglacial setting.

Heterogeneidad del tumor primario en la18F-FDG PET/TC pretratamiento para predecir el pronóstico en pacientes con cáncer de recto sometidos a cirugía tras terapia neoadyuvante / Primary tumor heterogeneity on pretreatment18F-FDG PET/CT to predict outcome in patients with rectal cancer who underwent surgery after neoadjuvant therapy

Objetivo Estudio retrospectivo cuyo objetivo fue investigar el valor de las características de textura de los tumores primarios en la PET/TC con 18F-FDG pretratamiento para la predicción de la respuesta al tratamiento, la progresión y la supervivencia global en pacientes con cáncer de recto que se sometieron a cirugía después de la terapia neoadyuvante (TNA). Métodos Se incluyeron en este estudio pacientes con cáncer de recto que se sometieron a estudio PET/TC con 18F-FDG antes del tratamiento y se sometieron a cirugía después de TNA. Se registraron las características clínico-patológicas, la fecha del último seguimiento, la evolución y fallecimiento. Los parámetros de las texturas y los convencionales de PET (Standard Uptake Value-SUVmax, volumen tumoral metabólico-MTV, glucólisis total de la lesión-TLG) se obtuvieron a partir de imágenes PET/TC utilizando el programa LifeX. Los parámetros se agruparon utilizando el índice de Youden en el análisis ROC. Los factores que predicen la respuesta patológica al tratamiento, la progresión y la supervivencia global se determinaron mediante regresión logística y análisis de regresión de Cox. Resultados Cuarenta y cuatro pacientes (26-59% hombres, 18-41% mujeres; 60,1 ± 11,4 años) con cáncer de recto fueron incluidos en este estudio. El número de pacientes respondedores y no respondedores a TNA fueron de 15 (34,9%) y 28 (65,1%), respectivamente. La mediana de la duración del seguimiento fue de 29,9 meses. 9 (20,5%) mostraron progresión de la enfermedad y 8 (18,2%) fallecieron durante el período de seguimiento. Los parámetros de entropía GLCM de diferencia y correlación GLCM se encontraron como predictores independientes para la respuesta a TNA. Los parámetros de positividad del margen quirúrgico, rango intercuartílico de intensidad CONV y textura AUC-CSHDISC fueron predictores independientes de progresión (AU)

Purpose This retrospective study aimed to investigate the value of texture features of primary tumors in pretreatment18F-FDG PET/CT in the prediction of response to treatment, progression, and overall survival in patients with rectal cancer who underwent surgery after neoadjuvant therapy (NAT). Method Patients with rectal cancer who had pretreatment18F-FDG PET/CT, and underwent surgery after NAT were included in this study. Clinicopathologic features, date of last follow-up, progression, and death were recorded. Textural and conventional PET parameters (maximum standardized uptake value-SUVmax, metabolic tumor volume-MTV, total lesion glycolysis-TLG) were obtained from PET/CT images using LifeX program. Parameters were grouped using Youden index in ROC analysis. Factors predicting the pathological response to treatment, progression, and overall survival were determined using logistic regression and Cox regression analyses. Results Forty-four patients (26(59%) male, 18 (41%) female; 60.1 ± 11.4 years) with rectal cancer were included in this study. The numbers of patients with responders and non-responders to NAT were15(34.9%) and 28(65.1%), respectively. One patient’ pathology report did not contain the response status to NAT. The median of follow-up duration was 29.9 months. 9(20.5%) showed disease progression, and 8(18.2%) died during the follow-up period. Difference entropy GLCM and correlation GLCM parameters were found as independent predictors for response to NAT. The positivity of surgical margin, intensity interquartile range CONV and AUC-CSHDISC texture parameters were independent predictors of progression, while normalized inverse difference GLCM and LZLGEGLZLM parameters were independent predictorsof mortality. Conclusion The texture parameters obtained from pretreatment18F-FDG PET/CT have presented a more robust predictive value than conventional parameters in patients with rectal cancer who underwent surgery after NAT (AU)

Social play behavior shapes the development of prefrontal inhibition in a region-specific manner.

Experience-dependent organization of neuronal connectivity is critical for brain development. We recently demonstrated the importance of social play behavior for the developmental fine-tuning of inhibitory synapses in the medial prefrontal cortex in rats. When these effects of play experience occur and if this happens uniformly throughout the prefrontal cortex is currently unclear. Here we report important temporal and regional heterogeneity in the impact of social play on the development of excitatory and inhibitory neurotransmission in the medial prefrontal cortex and the orbitofrontal cortex. We recorded in layer 5 pyramidal neurons from juvenile (postnatal day (P)21), adolescent (P42), and adult (P85) rats after social play deprivation (between P21 and P42). The development of these prefrontal cortex subregions followed different trajectories. On P21, inhibitory and excitatory synaptic input was higher in the orbitofrontal cortex than in the medial prefrontal cortex. Social play deprivation did not affect excitatory currents, but reduced inhibitory transmission in both medial prefrontal cortex and orbitofrontal cortex. Intriguingly, the reduction occurred in the medial prefrontal cortex during social play deprivation, whereas the reduction in the orbitofrontal cortex only became manifested after social play deprivation. These data reveal a complex interaction between social play experience and the specific developmental trajectories of prefrontal subregions.

European Society of Gynaecological Oncology Guidelines for the Management of Patients with Vulvar Cancer - Update 2023.

BACKGROUND: As part of its mission to improve the quality of care for women with gynecological cancers across Europe, the European Society of Gynaecological Oncology (ESGO) first published in 2017 evidence-based guidelines for the management of patients with vulvar cancer. OBJECTIVE: To update the ESGO guidelines based on the new evidence addressing the management of vulvar cancer and to cover new topics in order to provide comprehensive guidelines on all relevant issues of diagnosis and treatment of vulvar cancer. METHODS: The ESGO Council nominated an international development group comprised of practicing clinicians who provide care to vulvar cancer patients and have demonstrated leadership through their expertize in clinical care and research, national and international engagement and profile as well as dedication to the topics addressed to serve on the expert panel (18 experts across Europe). To ensure that the statements were evidence-based, new data identified from a systematic search were reviewed and critically appraised. In the absence of any clear scientific evidence, judgment was based on the professional experience and consensus of the international development group. Prior to publication, the guidelines were reviewed by 206 international practitioners in cancer care delivery and patient representatives. RESULTS: The updated guidelines cover comprehensively diagnosis and referral, staging, pathology, pre-operative investigations, surgical management (local treatment, groin treatment, sentinel lymph node procedure, reconstructive surgery), (chemo)radiotherapy, systemic treatment, treatment of recurrent disease (vulvar, inguinal, pelvic, and distant recurrences), and follow-up. Management algorithms are also defined.

The TNFR1 antagonist Atrosimab reduces neuronal loss, glial activation and memory deficits in an acute mouse model of neurodegeneration.

Tumor necrosis factor alpha (TNF-α) and its key role in modulating immune responses has been widely recognized as a therapeutic target for inflammatory and neurodegenerative diseases. Even though inhibition of TNF-α is beneficial for the treatment of certain inflammatory diseases, total neutralization of TNF-α largely failed in the treatment of neurodegenerative diseases. TNF-α exerts distinct functions depending on interaction with its two TNF receptors, whereby TNF receptor 1 (TNFR1) is associated with neuroinflammation and apoptosis and TNF receptor 2 (TNFR2) with neuroprotection and immune regulation. Here, we investigated the effect of administering the TNFR1-specific antagonist Atrosimab, as strategy to block TNFR1 signaling while maintaining TNFR2 signaling unaltered, in an acute mouse model for neurodegeneration. In this model, a NMDA-induced lesion that mimics various hallmarks of neurodegenerative diseases, such as memory loss and cell death, was created in the nucleus basalis magnocellularis and Atrosimab or control protein was administered centrally. We showed that Atrosimab attenuated cognitive impairments and reduced neuroinflammation and neuronal cell death. Our results demonstrate that Atrosimab is effective in ameliorating disease symptoms in an acute neurodegenerative mouse model. Altogether, our study indicates that Atrosimab may be a promising candidate for the development of a therapeutic strategy for the treatment of neurodegenerative diseases.

Factorial structure of the German Care Dependency Scale for self-assessment among older adults in supported housing.

AIM: To determine the factorial structure of the German Care Dependency Scale (CDS) for self-assessment in supported housing in Austria. BACKGROUND: The CDS is a well-established tool for the assessment of care dependency. However, several versions of the scale showed different factorial structures depending on the country and the setting where they were applied. The factorial structure of the CDS, therefore, needed clarification prior to its application in supported housing. DESIGN: Cross-sectional study. METHODS: Self-assessments of care dependency were obtained from residents in supported housing in Austria. The factorial structure of the scale was determined by exploratory factor analysis. The resulting factor models were compared by confirmatory factor analyses with a single factor model regarding the best fit. CDS total score and sum scores of the identified factors were correlated with externally assessed care levels according to the Austrian care insurance. RESULTS: 48.2% of the residents in supported housing participated, but some of them were younger than 60. Exploratory factor analysis resulted in a three-factor model with two variants in the distribution of items, depending on whether people over 59 were included in the analysis or not. The second variant showed the best fit in confirmatory factor analysis. CDS total score and sum scores of the identified factors showed statistically significant correlations with externally assessed care levels. CONCLUSION: The three-factorial structure differentiates between various aspects of support and results from the particular characteristics of the setting and the care recipients. Several cross-loadings of items indicate an ambiguous understanding of support needs. It is suggested to modify the scale to adapt it to the target group and setting. IMPLICATIONS FOR THE PROFESSION: Self-assessments with a modified version of CDS in supported housing can be useful to identify the various support needs in this setting. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.

Grambank reveals the importance of genealogical constraints on linguistic diversity and highlights the impact of language loss.

While global patterns of human genetic diversity are increasingly well characterized, the diversity of human languages remains less systematically described. Here, we outline the Grambank database. With over 400,000 data points and 2400 languages, Grambank is the largest comparative grammatical database available. The comprehensiveness of Grambank allows us to quantify the relative effects of genealogical inheritance and geographic proximity on the structural diversity of the world's languages, evaluate constraints on linguistic diversity, and identify the world's most unusual languages. An analysis of the consequences of language loss reveals that the reduction in diversity will be strikingly uneven across the major linguistic regions of the world. Without sustained efforts to document and revitalize endangered languages, our linguistic window into human history, cognition, and culture will be seriously fragmented.

Environmental Factors Linked to Reporting of Active Malaria Foci in Thailand.

Thailand has made substantial progress towards malaria elimination, with 46 of the country's 77 provinces declared malaria-free as part of the subnational verification program. Nonetheless, these areas remain vulnerable to the reintroduction of malaria parasites and the reestablishment of indigenous transmission. As such, prevention of reestablishment (POR) planning is of increasing concern to ensure timely response to increasing cases. A thorough understanding of both the risk of parasite importation and receptivity for transmission is essential for successful POR planning. Routine geolocated case- and foci-level epidemiological and case-level demographic data were extracted from Thailand's national malaria information system for all active foci from October 2012 to September 2020. A spatial analysis examined environmental and climate factors associated with the remaining active foci. A logistic regression model collated surveillance data with remote sensing data to investigate associations with the probability of having reported an indigenous case within the previous year. Active foci are highly concentrated along international borders, particularly Thailand's western border with Myanmar. Although there is heterogeneity in the habitats surrounding active foci, land covered by tropical forest and plantation was significantly higher for active foci than other foci. The regression results showed that tropical forest, plantations, forest disturbance, distance from international borders, historical foci classification, percentage of males, and percentage of short-term residents were associated with the high probability of reporting indigenous cases. These results confirm that Thailand's emphasis on border areas and forest-going populations is well placed. The results suggest that environmental factors alone are not driving malaria transmission in Thailand; rather, other factors, including demographics and behaviors that intersect with exophagic vectors, may also be contributors. However, these factors are syndemic, so human activities in areas covered by tropical forests and plantations may result in malaria importation and, potentially, local transmission, in foci that had previously been cleared. These factors should be addressed in POR planning.

Platin desensitizations in thoracic malignancies and risk factors for breakthrough reactions

Although platin desensitization is a safe and effective alternative for patients with hypersensitivity reactions (HSRs), sometimes breakthrough reactions (BTRs) can be encountered. However, data about the risk factors for BTRs are limited. The aim of this study is to define the outcomes of desensitization, the characteristics of BTRs, and to identify the risk factors for BTRs with platins in thoracic malignancies. This is a retrospective report of patients with thoracic malignancies who underwent platin desensitization. Patients’ demographics, initial HSR characteristics, skin test results, desensitization outcomes, and BTR characteristics were recorded. Thirty-three lung cancer and 14 malignant pleural mesothelioma (MPM) patients were included in the study. The culprit drug was cisplatin in 29 and was carboplatin in 18 patients. Skin test positivity was 43.5% with cisplatin, 50% with carboplatin, and it was found to be higher if the interval between the initial HSR and skin testing (ST) was ˃20 days (p = 0.027). One hundred and five desensitization courses were performed. Twenty-two patients had 33 BTRs. Skin test positivity was higher in the BTR-positive group (p = 0.025). BTRs (18.2%; n = 6) were more severe than initial HSR. In the case of epinephrine administration during initial HSR, epinephrine administration during the first BTR was found to be more (p = 0.036). The target dose was achieved in 92.4% of desensitization courses. The number of previous platin infusions ≥10 was found to be an independent risk factor for BTR development (p = 0.036 OR:17.641, 95% CI: 1.211–256.971). Identification of risk factors for BTR will guide appropriate management and desensitization approaches for platin HSRs (AU)

Phase II activity trial of high-dose radiation and chemosensitization in patients with macrometastatic lymph node spread after sentinel node biopsy in vulvar cancer: GROningen INternational Study on Sentinel nodes in Vulvar cancer III (GROINSS-V III/NRG-GY024).

BACKGROUND: Standard treatment of early-stage vulvar cancer is a radical, wide, local excision of the primary tumor and a sentinel lymph node (SLN) procedure for the groins. An inguinofemoral lymphadenectomy is no longer necessary for patients who have a negative SLN or micrometastasis (≤2 mm). When there is macrometastasis (>2 mm) in the SLN, an inguinofemoral lymphadenectomy is indicated; however, this procedure is associated with major morbidity, such as wound healing, lymphoceles, and lymphedema. PRIMARY OBJECTIVE: To investigate the safety of replacing inguinofemoral lymphadenectomy by chemoradiation in patients with early-stage vulvar cancer with a macrometastasis (>2 mm) and/or extracapsular extension in the sentinel node. STUDY HYPOTHESIS: Combination of 56 Gy of radiation to the inguinal site and concurrent cisplatin chemotherapy without completion inguinofemoral lymphadenectomy will be feasible and safe, with low groin recurrence rates. TRIAL DESIGN: This is a single-arm, prospective phase II treatment trial with stopping rules for unacceptable groin recurrences. Eligible patients will receive 56 Gy of radiation to the involved inguinal site and chemotherapy with concurrent cisplatin. MAJOR INCLUSION/EXCLUSION CRITERIA: Eligible patients undergoing sentinel node procedure will have stage I, unifocal, invasive (>1 mm depth of invasion) squamous cell carcinoma of the vulva with tumor size <4 cm, and no suspicious nodes on imaging. Those eligible for the trial are those with a metastasis >2 mm in the sentinel node and/or extracapsular extension, or more than one sentinel node with micrometastasis ≤2 mm. PRIMARY ENDPOINT: Groin recurrence rate in the first 2 years after primary treatment. SAMPLE SIZE: 157 patients with macrometastases in their SLN. ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: January 1, 2029. TRIAL REGISTRATION NUMBER: NCT05076942.