bluuebunny/crossref_metadata_2025_split huggingface dataset:
Climate change and resilience for antimicrobial stewardship and infection prevention
Authors: Abeles Shira R. , Kline Ahnika , Lee Pamela 
Published: June 2024

Purpose of review
This review covers recent research regarding the challenges posed by climate change within the areas of antimicrobial stewardship and infection prevention, and ways to build resiliency in these fields.

Recent findings
Infectious disease patterns are changing as microbes adapt to climate change and changing environmental factors. Capacity for testing and treating infectious diseases is challenged by newly emerging diseases, which exacerbate challenges to antimicrobial stewardship and infection prevention.
Antimicrobial resistance is accelerated due to environmental factors including air pollution, plastic pollution, and chemicals used in food systems, which are all impacted by climate change.
Climate change places infection prevention practices at risk in many ways including from major weather events, increased risk of epidemics, and societal disruptions causing conditions that can overwhelm health systems. Researchers are building resilience by advancing rapid diagnostics and disease modeling, and identifying highly reliable versus low efficiency interventions.

Summary
Climate change and associated major weather and socioeconomic events will place significant strain on healthcare facilities. Work being done to advance rapid diagnostics, build supply chain resilience, improve predictive disease modeling and surveillance, and identify high reliability versus low yield interventions will help build resiliency in antimicrobial stewardship and infection prevention for escalating challenges due to climate change.
Genomic Landscape of Adenocarcinomas Across the Gastroesophageal Junction
Authors: Nakauchi Masaya , Walch Henry S. , Nussenzweig Samuel , Carr Rebecca , Vos Elvira , Berger Michael F. , Schultz Nikolaus , Janjigian Yelena , Wu Abraham , Tang Laura , Shah Pari , Jones David R. , Coit Dan , Strong Vivian E. , Molena Daniela , Sihag Smita 
Published: June 2024

Objective:
To investigate how the Siewert classification of gastroesophageal junction adenocarcinomas correlates with genomic profiles.

Summary/Background Data:
Current staging and treatment guidelines recommend that tumors with an epicenter less than 2 cm into the gastric cardia be treated as esophageal cancers, while tumors with epicenter greater than 2 cm into the cardia be staged and treated as gastric cancers. To date, however, few studies have compared the genomic profiles of the 3 Siewert classification groups to validate this distinction.

Methods:
Using targeted tumor sequencing data on patients with adenocarcinoma of the gastroesophageal junction previously treated with surgery at our institution, we compared genomic features across Siewert classification groups.

Results:
A total of 350 patients were included: 121 had Siewert type I, 170 type II, and 59 type III. Comparisons by Siewert location revealed that Siewert type I and II were primarily characterized as the chromosomal instability (CIN) molecular subtype and displayed Barrett’s metaplasia and p53 and cell cycle pathway dysregulation. Siewert type III tumors, by contrast, were more heterogeneous, including higher proportions of microsatellite instability (MSI) and genomically stable (GS) tumors and more frequently displayed ARID1A and somatic CDH1 alterations, signet ring cell features, and poor differentiation. Overall, Siewert type I and II tumors demonstrated greater genomic overlap with lower esophageal tumors, while Siewert type III tumors shared genomic features with gastric tumors.

Conclusions:
Overall, our results support recent updates in treatment and staging guidelines. Ultimately, however, molecular rather than anatomic classification may prove more valuable in determining staging, treatment, and prognosis.
Graft Inflow Modulation by Splenic Artery Ligation for Portal Hyper Perfusion does not Decrease Rates of Early Allograft Dysfunction in Adult Live Donor Liver Transplantation
Authors: Pamecha Viniyendra , Tharun Gattu , Patil Nilesh , Mohapatra Nihar , Kumar Anubhav , Thapar Shalini , Sindwani Gaurav , Dhingra Udit , Yadav Anil 
Published: June 2024

Objective:
The primary objective was to compare the rates of early allograft dysfunction (EAD) in patients undergoing elective adult live donor liver transplantation (ALDLT) with and without graft portal inflow modulation (GIM) for portal hyper-perfusion. The secondary objectives were to compare time to normalization of bilirubin and International Normalized Ratio (INR), day 14 ascitic output more than 1liter, small-for-size syndrome (SFSS), intensive care unit / high dependency unit and total hospital stay, and 90 day morbidity and mortality.

Background:
GIM can prevent EAD in ALDLT patients with portal hyper-perfusion.

Methods:
A single-center randomized trial with and without GIM for portal hyper-perfusion by splenic artery ligation (SAL) in ALDLT was performed. After reperfusion, patients with portal venous pressure (PVP)>15 mm Hg with a gradient (PVP - central venous pressure) of ≥ 7 mm Hg and/or portal venous flow (PVF)>250 mL/min/100 grams of liver were randomized into two groups: GIM and No GIM.

Results:
75 of 209 patients satisfied the inclusion criteria, and 38 underwent GIM. Baseline PVF and PVP were comparable between the GIM and no GIM groups. SAL significantly reduced the PVF and PVP (P<0.001). There were no differences in the primary and secondary outcomes between the two groups. In the subgroup analysis, with a Graft to Recipient Weight Ratio (GRWR)≤0.8, there were no significant differences in the primary and secondary outcomes.

Conclusion:
SAL significantly decreased PVP and PVF, but did not decrease rates of EAD in adult LDLT.
The Effect of Intersectionality on Attrition among US General Surgery Trainees
Authors: Mesiti Andrea , Johnson Josh , Brouwer Julianna , Shui Amy M. , Yeo Heather , Sosa Julie Ann 
Published: June 2024

Objective:
To examine the association between intersectionality of race, ethnicity, and sex on retention of U.S. general surgery residents.

Summary Background Data:
There are limited data on the role that intersectionality plays on the US general surgery resident experience.

Methods:
Analysis was performed using Association of American Medical Colleges (AAMC) data for general surgery residents who started their training between 2005-2015 (followed through completion). Regression analyses were used to assess demographic associations with time to attrition or successful completion of residency training. Associations between faculty and resident demographics were assessed.

Results:
25,029 residents were included. Over the decade-long study period, the number of underrepresented in medicine (UIM) residents as a percentage of all residents remained similar from 17% to 19% (P=0.24). The percent of UIM males starting training in 2005 was 11% and 12% in 2015 (P-value=0.38). UIM females comprised 5.5% of trainees in 2005 and increased to 6.9% (P-value=0.003) in 2015; and female non-UIM residents increased from 23 to 28% (P-value<0.001). The overall rate of resident attrition was 15%. UIM females had the highest yearly attrition rate at 21% compared to non-UIM males at 13% (HR 1.7, P<0.001). UIM females were more likely to leave residency compared to UIM males (HR: 1.5; P<0.001). The percent of UIM faculty was positively correlated with percent of UIM residents (r=0.64, P<0.001).

Conclusions:
Increasing intersectionality is positively associated with attrition during surgery residency. The diversity of faculty appears to be associated with resident diversity.
End of life care for people with dementia and comorbid cancer: recent studies and research gaps
Authors: Surr Claire , Ashley Laura 
Published: June 2024

Purpose of review
This narrative review examines recent research on end of life (EOL) care for people with dementia and comorbid cancer, highlighting the complexity and challenge of providing effective EOL care for this group and areas of interest for future research.

Recent findings
People with cancer and dementia and their family/supporters have more complex care and support needs at EOL that are less well met than those of older adults with cancer alone, including questionable use of aggressive EOL care interventions, poorer access to specialist palliative care teams and poor pain management. Those diagnosed with dementia at the same time as, or after their cancer diagnosis, are at greater risk of aggressive EOL care and EOL cancer treatment and care plans that are not able to meet their care needs as dementia progresses.

Summary
There is a lack of research on EOL care for people with cancer and dementia. There is little understanding of what good care for this population looks like and if and how EOL care can best meet the needs of people with cancer and dementia or their carers/supporters. More research is needed to inform improved care for this population.
Genomic sequencing and neutralizing serological profiles during acute dengue infection: A 2017 cohort study in Nepal
Authors: Prajapati Sabita , Ngono Annie Elong , Cauley Melanie Mc , Timis Julia , Shrestha Srijan , Bastola Anup , Mandal Shrawan Kumar , Yadav Sanjay Ray , Napit Rajindra , Moi Meng Ling , Yamabhai Montarop , Sessions October M , Shresta Sujan , Manandhar Krishna Das 
Published: June 2024

AbstractDengue virus (DENV) is a mosquito-borne flavivirus that poses a threat to nearly 50% of the global population. DENV has been endemic in Nepal since 2006; however, little is known about how DENV is evolving or the prevalence of anti-DENV immunity within the Nepalese population. To begin to address these gaps, we performed a serologic and genetic study of 49 patients from across Nepal who presented at central hospitals during the 2017 dengue season with suspected DENV infection. Of the 49 subjects assessed, 21 (43%) were positive for DENV NS1 antigen; of these; 5 were also anti-DENV IgM+IgG+; 7 were DENV IgM+IgG−, 2 were IgM−IgG+, and 7 were IgM-IgG−by specific ELISAs. Seven of the 21 NS1+ sera were RNA+ by RT-PCR (six DENV2, one DENV3), suggesting that DENV2 was the dominant serotype in our cohort. Whole-genome sequencing of two DENV2 isolates showed similarity with strains circulating in Singapore in 2016, and the envelope genes were also similar to strains circulating in India in 2017. DENV-neutralizing antibodies (nAbs) were present in 31 of 47 sera tested (66%); among these, 20, 24, 26, and 12 sera contained nAbs against DENV1, 2, 3, and 4 serotypes, respectively. Serology analysis suggested that 12 (26%) and 19 (40%) of the 49 subjects were experiencing primary and secondary DENV infections, respectively. Collectively, our results provide evidence for current and/or past exposure to multiple DENV serotypes in our cohort, and the RNA analyses further indicate that DENV2 was the likely dominant serotype circulating in Nepal in 2017. These data suggest that expanded local surveillance of circulating DENV genotypes and population immunity will be important to effectively manage and mitigate future dengue outbreaks in Nepal.
Exploring Pathways to Compulsory Detention and Ways to Prevent Repeat Compulsory Detentions; Clinician Perspectives
Authors: Kular Ariana , Birken Mary , Wood Lisa , Parkinson Jordan , Bacarese-Hamilton Theresa , Blakley Louise , Hutchings-Hay Chloe , Nyikavaranda Patrick , Alam Dilshard , Ogbolu Raphael , Bendall Caroline , Tang Lai , Nickson Amy , Revell Cathryn , Mbeah-Bankas Henrietta , Mitchell Lizzie , Fraser Kathleen Lindsay , White Valerie Christina , Lobban Fiona , Lloyd-Evans Brynmor , Johnson Sonia 
Published: June 2024

AbstractBackgroundRates of compulsory detention in psychiatric hospitals have risen over several decades in England and some other higher income countries. This study explores clinicians’ perspectives on how service users come to be compulsorily detained in psychiatric hospitals and their suggestions for reducing these detentions in the future.MethodsSemi-structured qualitative interviews were conducted with 23 clinicians working with individuals who have been compulsorily detained under the Mental Health Act in England. Interviews were carried out by telephone or videoconference. Data were analysed using template analysis.ResultsThree major themes were identified, with multiple sub-themes (a) service user factors that increase risk of compulsory detention, including high levels of risk, previous/underlying trauma, medication non-adherence, service user perceptions of their mental health state, disadvantage and discrimination, and lack of stability and involvement from family and social networks; (b) service-level reasons for being detained, including lack of communication and continuity of care, historical inability to obtain trust and confidence from parts of population, clinician biases and assumptions, lack of resources, lack of treatment and care variety, and systemic/institutional barriers to engagement; and (c) ways to improve services to reduce compulsory detainment, including increasing quality of care and patient/family level interventions, investing in services, offer choice regarding medication, offer alternatives to compulsory detention, and improve discharge planning.ConclusionsFindings suggested clinicians see that at least some compulsory hospital admissions as avoidable, particularly through better resourced and more accessible services and changes in staff attitudes to address unconscious biases and promote collaborative care. Our findings provide a range of potential means to reduce detentions, which warrant development and testing in research and practice.
TYK2 as a novel therapeutic target in Alzheimer’s Disease with TDP-43 inclusions
Authors: König Laura E. , Rodriguez Steve , Hug Clemens , Daneshvari Shayda , Chung Alexander , Bradshaw Gary A. , Sahin Asli , Zhou George , Eisert Robyn J. , Piccioni Federica , Das Sudeshna , Kalocsay Marian , Sokolov Artem , Sorger Peter , Root David E. , Albers Mark W. 
Published: June 2024

SUMMARYNeuroinflammation is a pathological feature of many neurodegenerative diseases, including Alzheimer’s disease (AD)1,2and amyotrophic lateral sclerosis (ALS)3, raising the possibility of common therapeutic targets. We previously established that cytoplasmic double-stranded RNA (cdsRNA) is spatially coincident with cytoplasmic pTDP-43 inclusions in neurons of patients with C9ORF72-mediated ALS4. CdsRNA triggers a type-I interferon (IFN-I)-based innate immune response in human neural cells, resulting in their death4. Here, we report that cdsRNA is also spatially coincident with pTDP-43 cytoplasmic inclusions in brain cells of patients with AD pathology and that type-I interferon response genes are significantly upregulated in brain regions affected by AD. We updated our machine-learning pipeline DRIAD-SP (Drug Repurposing In Alzheimer’s Disease with Systems Pharmacology) to incorporate cryptic exon (CE) detection as a proxy of pTDP-43 inclusions and demonstrated that the FDA-approved JAK inhibitors baricitinib and ruxolitinib that block interferon signaling show a protective signal only in cortical brain regions expressing multiple CEs. Furthermore, the JAK family member TYK2 was a top hit in a CRISPR screen of cdsRNA-mediated death in differentiated human neural cells. The selective TYK2 inhibitor deucravacitinib, an FDA-approved drug for psoriasis, rescued toxicity elicited by cdsRNA. Finally, we identified CCL2, CXCL10, and IL-6 as candidate predictive biomarkers for cdsRNA-related neurodegenerative diseases. Together, we find parallel neuroinflammatory mechanisms between TDP-43 associated-AD and ALS and nominate TYK2 as a possible disease-modifying target of these incurable neurodegenerative diseases.
TNBC response to paclitaxel phenocopies interferon response which reveals cell cycle-associated resistance mechanisms
Authors: Calistri Nicholas L , Liby Tiera A. , Hu Zhi , Zhang Hongmei , Dane Mark , Gross Sean M. , Heiser Laura M. 
Published: June 2024

ABSTRACTPaclitaxel is a standard of care neoadjuvant therapy for patients with triple negative breast cancer (TNBC); however, it shows limited benefit for locally advanced or metastatic disease. Here we used a coordinated experimental-computational approach to explore the influence of paclitaxel on the cellular and molecular responses of TNBC cells. We found that escalating doses of paclitaxel resulted in multinucleation, promotion of senescence, and initiation of DNA damage induced apoptosis. Single-cell RNA sequencing (scRNA-seq) of TNBC cells after paclitaxel treatment revealed upregulation of innate immune programs canonically associated with interferon response and downregulation of cell cycle progression programs. Systematic exploration of transcriptional responses to paclitaxel and cancer-associated microenvironmental factors revealed common gene programs induced by paclitaxel, IFNB, and IFNG. Transcription factor (TF) enrichment analysis identified 13 TFs that were both enriched based on activity of downstream targets and also significantly upregulated after paclitaxel treatment. Functional assessment with siRNA knockdown confirmed that the TFs FOSL1, NFE2L2 and ELF3 mediate cellular proliferation and also regulate nuclear structure. We further explored the influence of these TFs on paclitaxel-induced cell cycle behavior via live cell imaging, which revealed altered progression rates through G1, S/G2 and M phases. We found that ELF3 knockdown synergized with paclitaxel treatment to lock cells in a G1 state and prevent cell cycle progression. Analysis of publicly available breast cancer patient data showed that high ELF3 expression was associated with poor prognosis and enrichment programs associated with cell cycle progression. Together these analyses disentangle the diverse aspects of paclitaxel response and identify ELF3 upregulation as a putative biomarker of paclitaxel resistance in TNBC.
Comparative analysis of the genomic architecture of six Fusarium species
Authors: Rau Domenico , Murgia Maria Leonarda , Fois Davide , Posadinu Chiara M. , Porceddu Andrea 
Published: June 2024

ABSTRACTComparative analyses of several plant pathogens have revealed that genome plasticity could be associated with different genomic architectures. In certain species, genomic compartments are characterised by highly conserved regions that contain mainly housekeeping genes and rearranged regions that are enriched for genes related to virulence and adaptation. The compositional and structural characteristics of genomic regions have been significantly associated with compartment membership in single species, but little information is available on the covariation of these features between species.Here, the results of a comparative analysis of the genomic architectures of six agriculturally relevantFusariumspecies, which differ for several biological and pathogenic characteristics, are presented. These includeF. culmorum,F. fujikoroi,F. graminearum, F. oxysporum,F. solani,andF. verticillioides.The genome sequences of these species were partitioned into adjacent windows, with the average level of gene collinearity with the other species used as an index of compartment membership. High collinearity is typical of conserved regions, while low collinearity is typical of rearranged regions. Several genic and genomic variables were found to be consistently associated with compartment definition among all theFusariumspecies that were investigated.The compartment that was characterised by lower collinearity (i.e., high genomic rearrangements) contained more relocated genes, species-specific genes and secreted protein-encoding genes than regions with low collinearity. Furthermore, several molecular evidence indicates that low-collinearity regions are more likely to be subjected to selective pressure than high-collinearity regions. Indeed, genes residing in the former regions exhibited higher rates of sequence evolution than in the latter, as indicated by the high non-synonymous-to-synonymous substitution rates.However, they exhibited signatures of selection to minimise the costs of transcription, as indicated by their high coding density. Our data suggests that although variable genomic compartments evolved mostly after species radiation, they share similar genomic features across related species and perhaps evolve with similar mechanisms.
The wondrous and worrying diversity of the N‐glycans ofChlorellafood supplements
Authors: Mócsai Réka , Helm Johannes , Polacsek Karin , Stadlmann Johannes , Altmann Friedrich 
Published: June 2024

AbstractN-glycans have recently emerged as highly varied elements ofChlorellastrains and products. Four years and many samples later, the ever-growing N-glycan diversity shall be revisited in the light of concepts of species definition and product authenticity. N-glycans of commercial products were analyzed by matrix-assisted time-of-flight mass spectrometry (MALDI-TOF MS) supported by chromatography on porous graphitic carbon with mass spectrometric detection. While 36% of 172 products were labeledC. vulgaris, only few had matching N-glycan patterns. 5 and 20 % of the products matched withC. sorokinianastrains SAG 211-8k and SAG 211-34, respectively, which, however, carry entirely different structures. 41 % presented with four frequently occurring glyco-types while 26 % of the samples showed unique or rare N-glycan patterns. The rest presented what could be taken as aC. vulgaristype N-glycan pattern. Identical masses derive from different structures in many cases. By no means do we want to question the presumed health benefits of the products or the honest intentions of manufacturers. We rather wish to raise awareness for the fascinating but also worrying variety of microalgal N-glycans and suggest it as a means for defining product identity and taxonomic assignments.
Comprehensive Model of Cell-to-Cell Cytokinin Transport Reveals A Specific Mode of Cytokinin Riboside Influx
Authors: Nedvěd Daniel , Hudeček Martin , Klíma Petr , Lacek Jozef , Müller Karel , Hošek Petr , Šmeringai Ján , Pernisová Markéta , Motyka Václav , Plíhal Ondřej , Hoyerová Klára 
Published: June 2024

1AbstractRibosylated forms of plant hormones cytokinins (CKs) are the dominant CK species translocated at long distances. Their particular roles in plant physiology imply the existence of a yet uncharacterized CK riboside-specific membrane transport system. In this work, we report significant differences in the kinetics of the membrane transport of CK nucleobases and ribosides and the overall affinity of membrane-bound carriers towards the two CK forms. We show that CK ribosides can inhibit the uptake of CK nucleobases in tobacco Bright Yellow 2 cell suspensions but not vice versa, confirming the existence of a membrane transport system that strictly recognizes CK ribosides.We further characterize the membrane transport of CK nucleobases and ribosides mediated by AtENT3 (EQULIBRATIVE NUCLEOSIDE TRANSPORTER 3), showing its preference towardstrans-zeatin riboside (tZR) over isopentenyl adenosine (iPR). With the molecular docking and molecular dynamics, we assess the interactions among the side chain of tZR and AtENT3 residues Tyr61 and Asp129, which are conserved in all AtENTs but not in the ENTs from non-plant species. Lastly, we show thatatent3mutation affects shoot phenotype, demonstrating the impact of CK riboside membrane transport on shoot development.