bluuebunny/crossref_metadata_2025_split huggingface dataset:
The potential role of cultural and religious healing practices in shaping community vulnerability to highly infectious diseases in western Kenya
Authors: Nga’ng’a Naomi , Momanyi Reuben Onkoba , Chemirmir Caleb , Biwott Hazael , Ayodo George , Orero Monica , Ochanda Damaris , Ngere Sarah , Ogola Winnie , Murundu Tutus , Munene Geoffrey , Misiani Zachary , Ayaibei Michael , Kiaka Richard Dimba 
Published: April 2024

AbstractWe draw from empirical research conducted in communities in three border counties in western Kenya – Homa Bay, Bungoma and West Pokot - to examine how cultural and religious beliefs and healing practices can potentially shape the vulnerability of those communities to highly infectious diseases. Fieldwork consisting of mixed methods namely, key informant interviews with traditional and religious healers as well as their patients, focus group discussions with community members knowledgeable on cultural customs and practices, and participatory inquiry workshops with health professionals and administrators were used to collect the data.We find that traditional and religious beliefs and healing practices potentially shape community vulnerability to highly infectious diseases in two major ways. First, is a dualistic illness etiology involving a biomedical and socio-cultural etiology. Unexplained illnesses and illnesses that did not respond to conventional medicine were treated using traditional medicine. Making traditional and religious healers the first mile treatment preference could potentially delay appropriate treatment and compromise safe handling in case the disease is highly infectious. Second aspect pertains to the risks in the traditional and spiritual healing practices. Shared consecrated water often fetched from a large water body, laying of hands, use of herbs and rituals involving slaughtering of animals enhanced contacts. The use of protective gears during healing was inconsistent among the healers, but largely lacking as many healers could not afford them or were considered to reduce patient’s faith in the healing powers. These practices potentially predispose people to highly infectious diseases and can hasten the spread and symptom severity. To reduce the vulnerability of border communities to highly infectious diseases, we argue for a need for comprehensive strategies that consider the intersecting factors of vulnerability to outbreaks, healing beliefs and practices. This may involve policy initiatives aimed at integrating traditional medicine practice and the mainstream health system.
Automated detection of large vessel occlusion using deep learning: a pivotal multicenter clinical trial and reader assessment study
Authors: Kim Jae Guk , Ha Sue Young , Kang You-Ri , Hong Hotak , Kim Dongmin , Lee Myungjae , Sunwoo Leonard , Ryu Wi-Sun , Kim Joon-Tae 
Published: April 2024

AbstractBackgroundThis multicenter clinical trial evaluated the stand-alone efficacy and the improvements in diagnostic accuracy of early-career physicians using a deep learning-based software to detect large vessel occlusion (LVO) in CT angiography (CTA).MethodsThis multicenter pivotal clinical trial included 595 ischemic stroke patients from January 2018 to September 2023. Standard reference and LVO locations (intracranial internal carotid artery [ICA], M1, or M2) were determined by consensus among three expert vascular neurologists after reviewing CTA, MR imaging, and symptom data. The performance of the JLK-LVO software was evaluated against a standard reference, and its impact on the diagnostic accuracy of four residents involved in stroke care was assessed. Performance metrics included the area under the receiver operating characteristic curve (AUROC), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV).ResultsAmong the 595 patients (mean age 68.5 ± 13.4 years, 56% male), 275 (46.2%) had LVO. The median time interval from the last known well moment to the CTA was 46 hours (IQR 11.8 to 64.4). For LVO detection, the software demonstrated a sensitivity of 86% and a specificity of 97%. For isolated M2 occlusions, it achieved a sensitivity of 69% and a specificity of 96%. The reader assessment study showed that reading with software assistance improved the sensitivity by 4.0% and AUROC by 2.4% (all p < 0.001) compared to readings without AI assistance.ConclusionThe software demonstrated a high detection rate for proximal LVO and moderate sensitivity for isolated MCA-M2 occlusion. In addition, the software improved diagnostic accuracy of early-career physicians in detecting LVO.
Ca2+-dependent phosphodiesterase 1 regulates the plasticity of striatal spiny projection neuron glutamatergic synapses
Authors: Zhai Shenyu , Otsuka Shintaro , Xu Jian , Clarke Vernon R. J. , Tkatch Tatiana , Wokosin David , Xie Zhong , Tanimura Asami , Agarwal Hitesh K. , Ellis-Davies Graham C. R. , Contractor Anis , Surmeier D. James 
Published: April 2024

SummaryLong-term synaptic plasticity at glutamatergic synapses on striatal spiny projection neurons (SPNs) is central to learning goal-directed behaviors and habits. Although considerable attention has been paid to the mechanisms underlying synaptic strengthening and new learning, little scrutiny has been given to those involved in the attenuation of synaptic strength that attends suppression of a previously learned association. Our studies revealed a novel, non-Hebbian, long-term, postsynaptic depression of glutamatergic SPN synapses induced by interneuronal nitric oxide (NO) signaling (NO-LTD) that was preferentially engaged at quiescent synapses. This form of plasticity was gated by local Ca2+influx through CaV1.3 Ca2+channels and stimulation of phosphodiesterase 1 (PDE1), which degraded cyclic guanosine monophosphate (cGMP) and blunted NO signaling. Consistent with this model, mice harboring a gain-of-function mutation in the gene coding for the pore-forming subunit of CaV1.3 channels had elevated depolarization-induced dendritic Ca2+entry and impaired NO-LTD. Extracellular uncaging of glutamate and intracellular uncaging of cGMP suggested that this Ca2+-dependent regulation of PDE1 activity allowed for local regulation of dendritic NO signaling. This inference was supported by simulation of SPN dendritic integration, which revealed that dendritic spikes engaged PDE1 in a branch-specific manner. In a mouse model of Parkinson’s disease (PD), NO-LTD was absent not because of a postsynaptic deficit in NO signaling machinery, but rather due to impaired interneuronal NO release. Re-balancing intrastriatal neuromodulatory signaling in the PD model restored NO release and NO-LTD. Taken together, these studies provide novel insights into the mechanisms governing NO-LTD in SPN and its role in psychomotor disorders, like PD.
The gut microbiome associated with LGI1- and CASPR2-antibody encephalitis
Authors: Gilbert Edmund , Binks Sophie , Damato Valentina , Uy Christopher , Colmenero Paula , Khalil Mohamed Ibrahim , O’Brien Marcus , Claesson Marcus , Cryan John F , Delanty Norman , Irani Sarosh R , Cavalleri Gianpiero L 
Published: April 2024

AbstractAutoimmune encephalitis is a cause of brain inflammation characterised by auto-antibodies which target cell surface neuronal proteins, and lead to neuronal dysfunction. In older people, common forms are encephalitis with autoantibodies to leucine-rich glioma inactivated protein 1 (LGI1) and contactin associated protein like 2 (CASPR2), whose presentation includes frequent focal seizures. The exact cause of these autoantibodies remain unknown, but established predispositions include overrepresented human leukocyte antigen (HLA) alleles. Yet, these alleles are themselves common in the healthy ancestry-matched population. One potential aetiological hypothesis is that an environmental trigger, such as the gut microbiome, interacts with a genetically predisposed individual. To investigate this, we studied 47 patients with leucine-rich glioma-inactivated 1 (LGI1)- or contactin-associated protein 2 (CAPSR2)-antibody encephalitis (LGI1/CASPR2-Ab-E) and 37 familial/environmentally matched controls, and performed metagenomic shotgun sequencing, to describe compositional and functional differences in the gut microbiome. We observed that LGI1/CASPR2-Ab-E gut microbiomes exhibited a significant reduction in the ratio ofFirmicutesandBacteroidetesphyla, which associated with dosage of HLA susceptibility alleles in LGI1-Ab-E patients. Furthermore, we identified differences in functional gene profiles in the gut microbiome that led to a reduction of neuroinflammatory protective short-chain-fatty-acids (SCFA) in LGI1-Ab-E patients. Taken together, our results suggest that a compositional shift in the gut microbiome of LGI1/CASPR2-Ab-E associates with a neuroinflammatory state, possibly through the reduction of SCFA production. Our study highlights the potential of the gut microbiome to explain some of the complex condition and unravel aetiological questions. Validation studies with greater sample sizes are recommended.
Climate-Sensitive Health Outcomes in Kenya: A Scoping Review of Environmental Exposures and Health Outcomes Research, 2000 – 2023
Authors: Gerard Jessica , Kibaara Titus , Blom Iris Martine , Falconer Jane , Mohammed Shamsudeen , Kadri-Alabi Zaharat , Taylor Roz , Abdullahi Leila , Hughes Robert C , Onyango Bernard , Brunn Ariel A 
Published: April 2024

AbstractClimate change threatens health and social development gains in Kenya, necessitating health policy planning for risk reduction and mitigation. To understand the baseline state of knowledge of environmental determinants of health in Kenya relevant to climate change, a comprehensive scoping review was undertaken. Compliant with a pre-registered protocol, nine bibliographic databases and grey literature sources were searched for articles published from 2000-2023. Two-stage screening was conducted on 17,394 articles; 635 full-texts were screened in duplicate. A final 353 articles underwent data extraction for topic categorisation, bibliometric analysis, and narrative summary. This was comprised of 344 (97%) journal articles, 59% of which were published after 2014 (n=207). Main study designs included observational (n=211) and modelling studies (n=64). Health topics centred on vector-borne diseases (41%, n=147), primarily vector abundance (n=102) and malaria (n=60), while injury or death (n=10), mental health conditions (n=7) and heat exposure (n=7) studies were less frequent. Environmental health research in Kenya is largely conducted in the Lake Victoria Basin, Rift Valley and Coastal regions, with fewer studies from the northern arid and semi-arid regions. Findings of this review suggest a growing and diverse field of predominantly observational research with an increasing focus on social determinants and policy-relevant themes, however research on vector-borne disease dwarfs other health outcomes and sparsely populated but climatically fragile regions are less represented in published literature. Addressing existing gaps in baseline evidence underpinning associations between the environment and health outcomes will benefit climate change attribution research and support future development of evidence-informed climate change and health policy in Kenya.
Multi-ancestry meta-analyses of lung cancer in the Million Veteran Program reveal novel risk loci and elucidate smoking-independent genetic risk
Authors: Gorman Bryan R. , Ji Sun-Gou , Francis Michael , Sendamarai Anoop K. , Shi Yunling , Devineni Poornima , Saxena Uma , Partan Elizabeth , DeVito Andrea K. , Byun Jinyoung , Han Younghun , Xiao Xiangjun , Sin Don D. , Timens Wim , Moser Jennifer , Muralidhar Sumitra , Ramoni Rachel , Hung Rayjean J. , McKay James D. , Bossé Yohan , Sun Ryan , Amos Christopher I. ,   VA Million Veteran Program, Pyarajan Saiju 
Published: April 2024

AbstractLung cancer remains the leading cause of cancer mortality, despite declines in smoking rates. Previous lung cancer genome-wide association studies (GWAS) have identified numerous loci, but separating the genetic risks of lung cancer and smoking behavioral susceptibility remains challenging. We performed multi-ancestry GWAS meta-analyses of lung cancer using the Million Veteran Program (MVP) cohort and a previous study of European-ancestry individuals, comprising 42,102 cases and 181,270 controls, followed by replication in an independent cohort of 19,404 cases and 17,378 controls. We further performed conditional meta-analyses on cigarettes per day and identified two novel, replicated loci, including the 19p13.11 pleiotropic cancer locus in LUSC. Overall, we report twelve novel risk loci for overall lung cancer, lung adenocarcinoma (LUAD), and squamous cell lung carcinoma (LUSC), nine of which were externally replicated. Finally, we performed phenome-wide association studies (PheWAS) on polygenic risk scores (PRS) for lung cancer, with and without conditioning on smoking. The unconditioned lung cancer PRS was associated with smoking status in controls, illustrating reduced predictive utility in non-smokers. Additionally, our PRS demonstrates smoking-independent pleiotropy of lung cancer risk across neoplasms and metabolic traits.
Plasma endostatin is an early creatinine independent predictor of acute kidney injury and need for renal replacement therapy in critical care
Authors: Koozi Hazem , Engström Jonas , Spångfors Martin , Friberg Hans , Frigyesi Attila 
Published: April 2024

AbstractPurposeEndostatin is a promising biomarker for predicting acute kidney injury (AKI) and mortality in the intensive care unit (ICU). We investigated plasma endostatin upon ICU admission as a predictor of AKI, renal replacement therapy (RRT), and 30-day mortality.MethodsA retrospective multicenter study was performed with admissions (ICU length of stay ≥24 hours) to four ICUs. KDIGO criteria defined AKI. Endostatin on ICU admission was compared to creatinine, cystatin C, and the Simplified Acute Physiology Score 3 (SAPS-3). Admissions with sepsis and creatinine <100 μmol/L on ICU admission underwent subgroup analyses. Regression models and the area under the receiver operating characteristic curve (AUC) were assessed.ResultsIn total, 4449 admissions were included (43% sepsis and 61% AKI). Endostatin was associated with AKI (odds ratio [OR] 1.6, 95% confidence interval [CI] 1.4-1.7), future AKI (OR 1.5, 95% CI 1.4-1.7), future AKI stage 3 (OR 1.4, 95% CI 1.2-1.6), and RRT (OR 1.2, 95% CI 1.1-1.4) independently of creatinine and cystatin C, with similar results in sepsis. Endostatin was also associated with time to AKI (hazard ratio 1.2, 95% CI 1.1-1.2). For admissions with creatinine <100 μmol/L, endostatin (AUC 0.62, 95% CI 0.59-0.65) outperformed creatinine (AUC 0.51, 95% CI 0.49-0.54) and cystatin C (AUC 0.53, 95% CI 0.50-0.56) in predicting future AKI (p<0.001). Endostatin was not associated with 30-day mortality after adjusting for SAPS-3.ConclusionEndostatin is an early and potentially clinically useful biomarker for predicting AKI and RRT needs at ICU admission, especially in patients with low to mildly elevated creatinine.
DBS-induced gamma entrainment as a new biomarker for motor improvement with neuromodulation
Authors: Mathiopoulou Varvara , Habets Jeroen , Feldmann Lucia K. , Busch Johannes L. , Roediger Jan , Behnke Jennifer K. , Schneider Gerd-Helge , Faust Katharina , Kühn Andrea A. 
Published: April 2024

AbstractFinely tuned gamma oscillations have been recorded from the subthalamic nucleus and cortex in Parkinson’s disease patients undergoing deep brain stimulation and are often associated with dyskinesia. More recently, it was shown that deep brain stimulation entrains finely tuned gamma to ½ of the stimulation frequency; however, the functional role of this signal is not yet fully understood.We recorded local field potentials from the subthalamic nucleus in 19 chronically implanted Parkinson’s disease patients under effective dopaminergic medication and during deep brain stimulation with increasing stimulation amplitude, while they were at rest and during repetitive hand movements. We analyzed the effect of stimulation intensity on gamma band 1:2 entrainment and compared the entrained signal during rest and during repetitive movement.Spontaneous finely tuned gamma was present in eight out of 19 patients (peak frequencyμ= 78.4 ±4.3 Hz). High-frequency deep brain stimulation induced 1:2 gamma entrainment in 15 out of 19 patients. Entrainment occurred at a mean stimulation amplitude of 2.2 0.75 mA and disappeared or decreased in power during higher stimulation amplitude in three patients. In patients with spontaneous finely tuned gamma, increasing the stimulation amplitude induced a progressive frequency shift of spontaneous finely tuned gamma until it locked to 1:2 entrainment. Only five out of 15 patients with entrained gamma activity showed dyskinesia during stimulation. Further, there was a significant increase in the power of 1:2 entrained gamma activity during movement in comparison to rest. Finally, patients with entrained gamma activity had faster movements as compared to those without gamma entrainment.These findings argue for a functional relevance of the stimulation-induced 1:2 gamma entrainment in Parkinson’s disease patients as a prokinetic activity that, however, is not necessarily promoting dyskinesia. Previously published electrophysiological models of entrainment fit well to our results and support our findings that stimulation-induced entrainment can be a promising real-life biomarker for closed-loop deep brain stimulation.
Low birthweight increased the risk of neonatal death twenty-folds in Northern Uganda: a community-based cohort study
Authors: Odongkara Beatrice , Nankabirwa Victoria , Achora Vincentina , Arach Anna Agnes , Napyo Agnes , Musaba Milton , Mukunya David , Ndeezi Grace , Tylleskär Thorkild , Tumwine James K 
Published: April 2024

AbstractBackgroundLow birthweight (LBW) is the leading cause of neonatal mortality and hospitalization worldwide. This study specifically aimed to: 1) determine the frequency of a) neonatal deaths and 2) assess their association with LBW in Northern Uganda.MethodsA cohort study, nested in the Survival Pluss cluster randomized trial (NCT02605369), was conducted from January 2018 to February 2019 in Lira district, Northern Uganda. Out of 1877 pregnant women, 1556 live-born infants had their birthweight measured and were followed up to 28 days after birth. Generalized estimation equation regression models of thePoissonfamily with a log link were used to calculate the risk ratios between LBW and death.ResultsThe risk of neonatal death was: 21/1,556 or 13.5 (95% CI: 8.8 – 20.6) per 1,000 live births. The respective sex and cluster adjusted proportion of neonatal death per 1000 live births among LBW, normal weight and not-weighed infants were 103 (95% CI: 47.2 – 212), 5.4 (95% CI: 2.1 – 13.9) and 167 (95% CI: 91.1-285). Compared to normal birthweight, LBW and not-weighed infants were each associated with a 20- and 30-folds increased risk of neonatal death.ConclusionIn this community-based cohort study in Northern Uganda, neonatal mortality was 13.5/1000 live births. In the LBW and not-weighed groups, the risk of a neonatal death were more than twenty-times that of non-LBW infants. Efforts to reduce the number of LBW infants and/or prevent adverse outcomes in this patient group urgently are needed. In addition, all babies with should have birthweight recorded to facilitate early risk identification and management.
Global mapping of theChlamydia trachomatisconventional secreted effector – host interactome reveals CebN interacts with nucleoporins and Rae1 to impede STAT1 nuclear translocation
Authors: Steiert Brianna , Andersen Shelby E. , McCaslin Paige N. , Elwell Cherilyn A. , Faris Robert , Tijerina Xavier , Smith Parker , Eldridge Quinn , Imai Brian S. , Arrington Justine V. , Yau Peter M. , Mirrashidi Kathleen M. , Johnson Jeffrey R. , Verschueren Erik , Von Dollen John , Jang Gwendolyn M. , Krogan Nevan J. , Engel Joanne N. , Weber Mary M. 
Published: April 2024

ABSTRACTChlamydia trachomatis(C.t.), the leading cause of bacterial sexually transmitted infections, employs a type III secretion system (T3SS) to translocate two classes of effectors, inclusion membrane proteins and conventional T3SS (cT3SS) effectors, into the host cell to counter host defense mechanisms. Here we employed three assays to directly evaluate secretion during infection, validating secretion for 23 cT3SS effectors. As bioinformatic analyses have been largely unrevealing, we conducted affinity purification-mass spectrometry to identify host targets and gain insights into the functions of these effectors, identifying high confidence interacting partners for 21 cT3SS effectors. We demonstrate that CebN localizes to the nuclear envelope in infected and bystander cells where it interacts with multiple nucleoporins and Rae1, blocking STAT1 nuclear import following IFN-γ stimulation. By building a cT3SS effector-host interactome, we have identified novel pathways that are targeted during bacterial infection and have begun to address howC.t.effectors combat cell autonomous immunity.
Efficient production of itaconic acid from the single carbon substrate methanol with engineeredKomagataella phaffii
Authors: Severinsen Manja Mølgaard , Bachleitner Simone , Modenese Viola , Ata Özge , Mattanovich Diethard 
Published: April 2024

AbstractBackgroundAmidst the escalating carbon dioxide levels resulting from fossil fuel consumption, there is a pressing need for sustainable, bio-based alternatives to underpin future global economies. Single carbon feedstocks, derived from CO2, represent promising substrates for biotechnological applications. Especially methanol is gaining prominence for bio-production of commodity chemicals.ResultsIn this study, we show the potential ofKomagataella phaffiias a production platform for itaconic acid using methanol as the carbon source. Successful integration of heterologous genes fromAspergillus terreus(cadA,mttAandmfsA) alongside fine-tuning of themfsAgene expression, led to promising initial itaconic acid titers of 28 g·L-1after five days of fed-batch cultivation. Through the combined efforts of process optimization and strain engineering strategies we further boosted the itaconic acid production reaching titers of 55 g·L-1after less than five days of methanol feed, whilst increasing the product yield on methanol from 0.06 g·g-1to 0.24 g·g-1.ConclusionOur results highlight the potential ofK. phaffiias a methanol-based platform organism for sustainable biochemical production.
The fine-tuning of synapse development by oxidative stress and autophagy requires presynaptic ATM kinase
Authors: Taylor Matthew J. , Ahmed Syed Azan , Badenoch Ellena G. , Bennett David , Tuxworth Richard I. 
Published: April 2024

AbstractTwo processes held in delicate balance during the fine tuning of synapse development are oxidative stress and autophagy: each can promote synapse expansion yet in excess are toxic. How this balance is maintained is not fully understood. While ataxia-telangiectasia mutated (ATM) is recognized as a key regulator of the DNA damage response, there is increasing evidence of a neuronal-specific role for this ubiquitous kinase and deficiency causes early-onset neurodegeneration. We report a requirement for presynapticDrosophilaATM (dATM) in neurodevelopment that is independent of its functions in the DNA damage response. Reduction of presynapticdATMexpression causes hypersensitivity to raised oxidative stress and a failure to induce autophagy which leaves mitochondria in excess in neurons. We demonstrate that presynaptic dATM coordinates autophagy through the conserved ATM-AMPK axis. Similarly to mammalian ATM, neuronal dATM is predominantly cytosolic and forms synaptic foci. dATM also colocalizes with autophagosomes. We propose a model wherein dATM responds to increased reactive oxygen species resulting from heightened neuronal activity by activating autophagy to induce synaptic growth, while protecting the neuron from excitotoxicity and oxidative stress.