bluuebunny/crossref_metadata_2025 huggingface dataset:
Quantification of Parkinsonian unilateral involvement from ocular fixational patterns using a deep video representation
Authors: Olmos Juan , Valenzuela Brayan , Martínez Fabio
Published: October 2023

Purpose

Lateralisation of motor symptoms is a prevalent characteristic of Parkinson’s disease (PD). Hence, unilateral involvement is crucial for personalized treatments and measuring therapy effectiveness. Nonetheless, most motor symptoms, including lateralization, are mainly evident at advanced stages of the disease. Recently, ocular fixation instability emerged as a promising PD biomarker with a high sensitivity to discriminate PD. We hypothesize that unilateral involvement can be recovered from the assessment and quantification of PD-related ocular abnormalities.

Methods

This method proposes a computer-based strategy to quantify PD lateralization from ocular fixation patterns. The method follows a markerless strategy fed by slices with spatiotemporal eye movement information. A deep convolutional model was used to discriminate between PD and a control population. Additionally, model prediction probabilities were analyzed to select the dominant eye associated with unilateral involvement.

Results

The proposed approach reports an average accuracy of 91.92% classifying PD. Interestingly, using the dominant side, the approach achieves an average PD prediction probability of 93.3% (95% CI: [91.61,95.07]), evidencing capabilities to capture the most affected side. Besides, the reported results strongly correlate with the disease, even for patients categorized at early stages. A low-dimensional projection tool was used to support the classification results by finding a 2d space that eases the discrimination among classes.

Conclusions

The strategy is sensitive to detecting and classifying PD fixational patterns and determining the side with major impairments. This approach may be a potential tool to support the characterization of the disease and as an alternative to defining personalized treatments.
Supercongruences involving Domb numbers and binary quadratic forms
Authors: Mao Guo-Shuai , Schlosser Michael J.
Published: October 2023

In this paper, we prove two recently conjectured supercongruences (modulo $$p^3$$

p
3

, where p is any prime greater than 3) of Zhi-Hong Sun on truncated sums involving the Domb numbers. Our proofs involve a number of ingredients such as congruences involving specialized Bernoulli polynomials, harmonic numbers, binomial coefficients, and hypergeometric summations and transformations.
Automated blood glucose regulation for nonlinear model of type-1 diabetic patient under uncertainties: GWOCS type-2 fuzzy approach
Authors: Elhoushy Mohanad , Zalam Belal A. , Sayed Amged , Nabil Essam
Published: October 2023

Regulating blood glucose level (BGL) for type-1 diabetic patient (T1DP) accurately is very important issue, an uncontrolled BGL outside the standard safe range between 70 and 180 mg/dl results in dire consequences for health and can significantly increase the chance of death. So the purpose of this study is to design an optimized controller that infuses appropriate amounts of exogenous insulin into the blood stream of T1DP proportional to the amount of obtained glucose from food. The nonlinear extended Bergman minimal model is used to present glucose-insulin physiological system, an interval type-2 fuzzy logic controller (IT2FLC) is utilized to infuse the proper amount of exogenous insulin. Superiority of IT2FLC in minimizing the effect of uncertainties in the system depends primarily on the best choice of footprint of uncertainty (FOU) of IT2FLC. So a comparison includes four different optimization methods for tuning FOU including hybrid grey wolf optimizer-cuckoo search (GWOCS) and fuzzy logic controller (FLC) method is constructed to select the best controller approach. The effectiveness of the proposed controller was evaluated under six different scenarios of T1DP using Matlab/Simulink platform. A 24-h scenario close to real for 100 virtual T1DPs subjected to parametric uncertainty, uncertain meal disturbance and random initial condition showed that IT2FLC accurately regulate BGL for all T1DPs within the standard safe range. The results indicated that IT2FLC using GWOCS can prevent side effect of treatment with blood-sugar-lowering medication. Also stability analysis for the system indicated that the system operates within the stability region of nonlinear system.
Facets of Impulsivity in Gaming Disorder: a Narrative Review
Authors: Müller Silke M. , Antons Stephanie , Brand Matthias
Published: October 2023

Purpose of review

This narrative review provides a detailed look at impulsivity in the context of gaming disorder. Summarizing empirical findings, we aim to identify whether gaming disorder is associated with specific facets of impulsivity, namely motor, attentional, and decisional impulsivity, assessed by self-report and behavioral measures. Wherever possible, we distinguished between general and stimuli-specific (gaming-related) impulsivity.

Recent findings

Gaming disorder is associated with attentional impulsivity. Heightened motor impulsivity in individuals with gaming disorder is particularly evident in the presence of gaming-related cues. Decisional impulsivity is not per se increased. Gender-related differences and comorbid ADHD are likely to moderate the association between impulsivity and gaming disorder symptoms.

Facets of impulsivity are differentially associated with gaming disorder. These associations are dependent upon characteristics of the studied population, used measures, and applied diagnostic criteria. Uniform diagnosis/screening and more targeted investigations are necessary in order to derive effective clinical implications.
Pre-existing chronic kidney disease, aetiology of acute kidney injury and infection do not affect renal outcome and mortality
Authors: Buckenmayer Anna , Siebler Nadja , Haas Christian S.
Published: October 2023

Background

We aimed to study the role of aetiology, pre-existing chronic kidney disease (CKD) and infections in acute kidney injury (AKI) on renal outcome and mortality.

Methods

This retrospective study analysed patients with AKI admitted to a university nephrology department from January 1st, 2020 through December 31st, 2020. Aetiology of AKI, underlying renal disease in case of pre-existing CKD and presence of infections were assessed. Development of renal function and risk of death were studied with follow-up until January 31st, 2023.

Results

Of 1402 patients screened, 432 patients (30.8%, 67.9 ± 15.4 years) fulfilled the inclusion criteria, half of the population presented with advanced CKD. Even though CKD patients were more often in need of chronic dialysis at time of discharge (6.9% vs 4.5%, p < .001), duration of hospital stay was shorter and in-hospital mortality tended to be lower when compared to AKI without prior renal disease. Neither aetiology of AKI nor pre-existing CKD had an impact on the combined endpoint of end-stage kidney disease and mortality (log rank 0.433 and 0.909). Overall, septic patients showed the highest in-hospital mortality (23.5%) and longest hospital stay (30.0 ± 22.8 days, p < .001), while patients with urosepsis had the shortest hospitalisation time (9.7 days) with lowest risk for dialysis (4.4%). Of note, outcome did not differ in patients with AKI when considering the infectious status.

Conclusions

Overall renal outcome and mortality in AKI patients were not affected by the cause of AKI, pre-existent CKD or infectious status. Only severity of AKI had a negative impact on outcome.

Graphical abstract
Stability and certain $$\mathbb {P}^n$$-functors
Authors: Reede Fabian
Published: October 2023

Let X be a K3 surface. We prove that Addington’s $$\mathbb {P}^n$$

P

n

-functor between the derived categories of X and the Hilbert scheme of points $$X^{[k]}$$

X

[
k
]

maps stable vector bundles on X to stable vector bundles on $$X^{[k]}$$

X

[
k
]

, given some numerical conditions are satisfied.
Mobility outcomes and associated factors of acute geriatric care in hospitalized older patients: results from the PAGER study
Authors: Werner Christian , Bauknecht Laura , Heldmann Patrick , Hummel Saskia , Günther-Lange Michaela , Bauer Jürgen M. , Hauer Klaus
Published: October 2023

Purpose

To examine distinct mobility outcomes (locomotor capacity, physical activity, life-space mobility) of acute geriatric care (AGC) in acutely hospitalized older adults and identify predictors associated with these outcomes.

Methods

The PAGER study was designed as a prospective observational study. Mobility outcomes of 107 hospitalized older patients (age = 83.2 ± 6.4 years, female: n = 68, 63.6%) receiving AGC were measured at hospital admission and discharge. Locomotor capacity was assessed with the Short Physical Performance Battery (SPPB), 24-h physical activity (step count) with an activity monitor, and life-space mobility with the Life-Space Assessment in Institutionalized Settings (LSA-IS). Baseline demographical, clinical, physical, cognitive, and psychological characteristics were analyzed as candidate predictors of mobility outcomes.

Results

SPPB (median [interquartile range] 4.0 [2.8–5.0] pt. vs. 5.0 [3.0–6.3] pt.), step count (516 [89–1806] steps vs. 1111 [228–3291] steps), and LSA-IS total score (10.5 [6.0–15.0] pt. vs. 16.3 [12.0–24.1] pt.) significantly improved during AGC (all p < 0.001). Adjusting for baseline status, frailty was identified as an independent negative predictor of SPPB, step count, and LSA-IS at discharge (p = 0.003–0.005). Barthel Index was also independently positively associated with step count (p = 0.017) at discharge, as was the mean daily PA level with SPPB (p = 0.027) at discharge, both independent of baseline status.

Conclusion

AGC improves distinct mobility outcomes in hospitalized older patients. Frailty was consistently found to be an independent negative predictor of all mobility outcomes. Frailty assessment in AGC may be important to identify patients at risk for decreased treatment gains in mobility. Early PA promotion in AGC seems to be beneficial in improving patients’ locomotor capacity.
CHronic hypERtension and L-citRulline studY (CHERRY): an Early-Phase Randomised Controlled Trial in Pregnancy
Authors: Ormesher Laura , Worton Stephanie A. , Best Ashley , Dodd Susanna R. , Dempsey Alice , Cottrell Elizabeth C. , Glossop Heather , Chmiel Catherine , Wu Hoi Yee , Hardwick Ben , Hennessy Sophie , Johnstone Edward D. , Myers Jenny E.
Published: October 2023

Oral supplementation with L-citrulline, which is sequentially converted to L-arginine then nitric oxide, improves vascular biomarkers and reduces blood pressure in non-pregnant, hypertensive human cohorts and pregnant mice with a pre-eclampsia-like syndrome. This early-phase randomised feasibility trial assessed the acceptability of L-citrulline supplementation to pregnant women with chronic hypertension and its effects on maternal BP and other vascular outcomes. Pregnant women with chronic hypertension were randomised at 12–16 weeks to receive 3-g L-citrulline twice daily (n = 24) or placebo (n = 12) for 8 weeks. Pregnant women reported high acceptability of oral L-citrulline. Treatment increased maternal plasma levels of citrulline, arginine and the arginine:asymmetric dimethylarginine ratio, particularly in women reporting good compliance. L-citrulline had no effect on diastolic BP (L-citrulline: − 1.82 95% CI (− 5.86, 2.22) vs placebo: − 5.00 95% CI (− 12.76, 2.76)), uterine artery Doppler or angiogenic biomarkers. Although there was no effect on BP, retrospectively, this study was underpowered to detect BP changes < 9 mmHg, limiting the conclusions about biological effects. The increase in arginine:asymmetric dimethylarginine ratio was less than in non-pregnant populations, which likely reflects altered pharmacokinetics of pregnancy, and further pharmacokinetic assessment of L-citrulline in pregnancy is advised.

Trial Registration EudraCT 2015-005792-25 (2017-12-22) and ISRCTN12695929 (2018-09-20)

Graphical Abstract

In pregnant women with chronic hypertension, L-citrulline is an acceptable intervention which increased plasma L-citrulline bioavailability but did not affect BP, potentially due to altered pharmacokinetics of pregnancy.
Student Development Theory and the Transformation of Student Affairs in the 1970s
Authors: McNeely Ian F.
Published: October 2023

Student development theory (SDT) is a diverse corpus of academic and popular psychology with real-world application to the maturation of college and university students. It originated during the campus upheavals of the 1960s as part of a collective effort to reconcile restive students to mass higher education and modern technological society. Then, in the 1970s, SDT was implemented and refined by an ambitious generation of student affairs professionals eager for institutional influence and academic legitimacy. By providing an animating moral and intellectual purpose to the bureaucratic sundering of student affairs divisions from academic affairs divisions, SDT abetted a lasting institutional and cultural change in the organization of the modern university circa 1970. As a discourse of therapeutic empowerment, SDT has had an enduring influence on the daily practice of student affairs administration in the five decades since.
Compressible turbulent convection in highly stratified adiabatic background
Authors: Panickacheril John John , Schumacher Jörg
Published: October 2023

Buoyancy-driven turbulent convection leads to a fully compressible flow with a prominent top-down asymmetry of first- and second-order statistics when the adiabatic equilibrium profiles of temperature, density and pressure change very strongly across the convection layer. The growth of this asymmetry and the formation of an increasingly thicker stabilized sublayer with a slightly negative mean convective heat flux$J_c(z)$at the top of the convection zone is reported here by a series of highly resolved three-dimensional direct numerical simulations beyond the Oberbeck–Boussinesq and anelastic limits for dimensionless dissipation numbers,$0.1 \le D\le 0.8$, at fixed Rayleigh number$Ra=10^6$and superadiabaticity$\epsilon =0.1$. The highly stratified compressible convection regime appears for$D > D_{crit}\approx 0.65$, when density fluctuations collapse to those of pressure; it is characterized by an up to nearly 50 % reduced global turbulent heat transfer and a sparse network of focused thin and sheet-like thermal plumes falling through the top sublayer deep into the bulk.
Development, Inc.? The EEC, Britain, Post-Colonial Overseas Development Aid, and Business
Authors: Dimier Véronique , Stockwell Sarah
Published: October 2023

This article assesses the “business of development” in the post-colonial age, when bilateral and multilateral aid regimes offered businesses new opportunities. It uses the case study of Britain and the European Economic Community (EEC), from Britain's accession to the EEC in 1973 to the early 1980s, to demonstrate that the British government viewed multilateral aid instruments, in particular the European Development Fund (EDF), as offering commercial opportunities for British firms. Based on records of the EEC, business associations, and the French and British states, the article analyzes business-state relationships between national governments, corporations, and supranational institutions. As the UK government tried to redirect EEC aid toward places where its firms had the most to gain, it met the opposition of other member states and European institutions as well as the disinterest of its own businesses.
Molecular evidence for the first records and range extension of the great seahorse (Hippocampus kelloggi, Jordan & Snyder, 1901) in Quelimane, central coast of Mozambique
Authors: Muhala Valdemiro , Guimarães-Costa Aurycéia , Macate Isadola Eusébio , Watanabe Luciana , de Sousa Rodrigo Petry Corrêa , Rocha Guilhermina , Carneiro Jeferson , Vallinoto Marcelo , Sampaio Iracilda
Published: October 2023

The family Syngnathidae contains 52 seahorse species, which inhabit a range of habitats including coral reefs, seagrass beds and coastal estuaries. The seahorse Hippocampus kelloggi is among the most widely distributed species, occurring from Indo-West Pacific to East Africa. This species was included in the IUCN Red List in 2017 and is classified as vulnerable according to A2cd criteria. In this study, three specimens collected from the central coast of Mozambique were investigated and based on morphology and mitochondrial subunit of cytochrome oxidase I (COI) were identified as H. kelloggi. These results confirmed for the first time the extensive range of occurrence of H. kelloggi on the central coast of Mozambique.
The March on Washington Movement, the Fair Employment Practices Committee, and the Long Quest for Racial Justice
Authors: Milkis Sidney , Rader Katherine
Published: October 2023

In the summer of 1941, the March on Washington Movement (MOWM), led by the civil rights and labor leader A. Philip Randolph, planned to march tens of thousands of African Americans on Washington, DC, to pressure President Franklin Roosevelt to abolish discrimination in the federal government and defense industries. After intensive negotiations, Roosevelt issued Executive Order 8802, banning those forms of discrimination and creating a federal agency to oversee this work: the Fair Employment Practices Committee (FEPC). Randolph and his allies use of pioneering pressure tactics coincided with a critical period of institutionalization of the modern presidency, ultimately resulting in executive action that significantly advanced civil rights and economic opportunity for Black Americans. Many scholars, focusing only on civil rights activists’ fraught relationship with Roosevelt and the Southern Democrats’ stubborn defense of Jim Crow in Congress and the states, have seen the highly contentious battles over the authority and policies of the FEPC as constituting a major defeat for MOWM’s state-centered civil rights strategy. Yet Randolph and his allies continued to believe that the most practical path to reform ran through the executive branch. In this article, we draw a contrast between the actions first taken by President Roosevelt with his wavering commitment to the FEPC and the stronger and more definitive actions taken by President Truman to desegregate the military and civil service, which broke open public-sector employment for African Americans. Beyond strategic considerations, the New Deal expansion of jobs in the national service and military made the modern executive an essential target of Randolph’s campaign to join the battles for civil rights with economic freedoms. Randolph’s decision to focus on employment in the rapidly expanding defense industries, federal workforce, and military thus marked a critical episode in the fight for the economic rights of Black Americans.
Methadone dose escalation in patients with opioid use disorder and cancer as a strategy for controlling cancer-related pain: A case series
Authors: Carli Marco , Fini Elisabetta , De Luca Giulia , Scarselli Marco , Lamanna Francesco , Vico Tiziana , Bocci Guido
Published: October 2023

Objectives

Opioid use disorder (OUD) and cancer gained attention as co-occurring diseases in the last 2 decades due to the possible relationship between opioid prescriptions for cancer pain and the risk of developing substance use disorder in cancer patients. However, little is known about patients previously diagnosed with OUD who develop cancer and how to manage both OUD symptoms and control pain.

Methods

The present case series deals with this subpopulation and proposes a dose escalation of methadone to control both the cancer-related pain and drug addiction symptoms.

Results

This approach is peculiar because methadone is not used as a first-line treatment in cancer pain management and is not often used as a second-line treatment as well. Our 4 patients experienced good clinical control of symptoms and no major adverse reactions.

Significance of results

The subgroup of patients with OUD who develop cancer could be the perfect population to reconsider the use of methadone as a first-line treatment for cancer pain. Prospective studies are needed to evaluate the efficacy and safety of increasing doses of methadone in these patients to validate our clinical approach.
Molecular response assessment using circulating tumor DNA (ctDNA) in advanced solid tumors
Authors: Thompson Jeffrey C. , Scholes Dylan G. , Carpenter Erica L. , Aggarwal Charu
Published: October 2023

The therapeutic landscape for patients with advanced malignancies has changed dramatically over the last twenty years. The growing number of targeted therapies and immunotherapeutic options available have improved response rates and survival for a subset of patients, however determining which patients will experience clinical benefit from these therapies in order to avoid potential toxicities and reduce healthcare costs remains a clinical challenge. Cell-free circulating tumor DNA (ctDNA) is shed by tumor cells into systemic circulation and is already an integral part of routine clinical practice for the non-invasive tumor genotyping in advanced non-small cell lung cancer as well as other malignancies. The short half-life of ctDNA offers a unique opportunity to utilize early on-treatment changes in ctDNA for real-time assessment of therapeutic response and outcome, termed molecular response. Here, we provide a summary and review of the use of molecular response for the prediction of outcomes in patients with advanced cancer, including the current state of science, its application in clinic, and next steps for the development of this predictive tool.
An end-to-end pipeline for succinic acid production at an industrially relevant scale using Issatchenkia orientalis
Authors: Tran Vinh G. , Mishra Somesh , Bhagwat Sarang S. , Shafaei Saman , Shen Yihui , Allen Jayne L. , Crosly Benjamin A. , Tan Shih-I , Fatma Zia , Rabinowitz Joshua D. , Guest Jeremy S. , Singh Vijay , Zhao Huimin
Published: October 2023

Microbial production of succinic acid (SA) at an industrially relevant scale has been hindered by high downstream processing costs arising from neutral pH fermentation for over three decades. Here, we metabolically engineer the acid-tolerant yeast Issatchenkia orientalis for SA production, attaining the highest titers in sugar-based media at low pH (pH 3) in fed-batch fermentations, i.e. 109.5 g/L in minimal medium and 104.6 g/L in sugarcane juice medium. We further perform batch fermentation using sugarcane juice medium in a pilot-scale fermenter (300×) and achieve 63.1 g/L of SA, which can be directly crystallized with a yield of 64.0%. Finally, we simulate an end-to-end low-pH SA production pipeline, and techno-economic analysis and life cycle assessment indicate our process is financially viable and can reduce greenhouse gas emissions by 34–90% relative to fossil-based production processes. We expect I. orientalis can serve as a general industrial platform for production of organic acids.
Retrosynthesis prediction with an interpretable deep-learning framework based on molecular assembly tasks
Authors: Wang Yu , Pang Chao , Wang Yuzhe , Jin Junru , Zhang Jingjie , Zeng Xiangxiang , Su Ran , Zou Quan , Wei Leyi
Published: October 2023

Automating retrosynthesis with artificial intelligence expedites organic chemistry research in digital laboratories. However, most existing deep-learning approaches are hard to explain, like a “black box” with few insights. Here, we propose RetroExplainer, formulizing the retrosynthesis task into a molecular assembly process, containing several retrosynthetic actions guided by deep learning. To guarantee a robust performance of our model, we propose three units: a multi-sense and multi-scale Graph Transformer, structure-aware contrastive learning, and dynamic adaptive multi-task learning. The results on 12 large-scale benchmark datasets demonstrate the effectiveness of RetroExplainer, which outperforms the state-of-the-art single-step retrosynthesis approaches. In addition, the molecular assembly process renders our model with good interpretability, allowing for transparent decision-making and quantitative attribution. When extended to multi-step retrosynthesis planning, RetroExplainer has identified 101 pathways, in which 86.9% of the single reactions correspond to those already reported in the literature. As a result, RetroExplainer is expected to offer valuable insights for reliable, high-throughput, and high-quality organic synthesis in drug development.
Broad and colossal edge supercurrent in Dirac semimetal Cd3As2 Josephson junctions
Authors: Chu Chun-Guang , Chen Jing-Jing , Wang An-Qi , Tan Zhen-Bing , Li Cai-Zhen , Li Chuan , Brinkman Alexander , Xiang Peng-Zhan , Li Na , Pan Zhen-Cun , Lu Hai-Zhou , Yu Dapeng , Liao Zhi-Min
Published: October 2023

Edge supercurrent has attracted great interest recently due to its crucial role in achieving and manipulating topological superconducting states. Proximity-induced superconductivity has been realized in quantum Hall and quantum spin Hall edge states, as well as in higher-order topological hinge states. Non-Hermitian skin effect, the aggregation of non-Bloch eigenstates at open boundaries, promises an abnormal edge channel. Here we report the observation of broad edge supercurrent in Dirac semimetal Cd3As2-based Josephson junctions. The as-grown Cd3As2 nanoplates are electron-doped by intrinsic defects, which enhance the non-Hermitian perturbations. The superconducting quantum interference indicates edge supercurrent with a width of ~1.6 μm and a magnitude of ~1 μA at 10 mK. The wide and large edge supercurrent is inaccessible for a conventional edge system and suggests the presence of non-Hermitian skin effect. A supercurrent nonlocality is also observed. The interplay between band topology and non-Hermiticity is beneficial for exploiting exotic topological matter.
Repressed Blautia-acetate immunological axis underlies breast cancer progression promoted by chronic stress
Authors: Ye Ling , Hou Yuanlong , Hu Wanyu , Wang Hongmei , Yang Ruopeng , Zhang Qihan , Feng Qiaoli , Zheng Xiao , Yao Guangyu , Hao Haiping
Published: October 2023

Chronic stress is a known risk factor for breast cancer, yet the underlying mechanisms are unclear. This study explores the potential involvement of microbial and metabolic signals in chronic stress-promoted breast cancer progression, revealing that reduced abundances of Blautia and its metabolite acetate may contribute to this process. Treatment with Blautia and acetate increases antitumor responses of CD8+ T cells and reverses stress-promoted breast cancer progression in female mice. Patients with depression exhibit lower abundances of Blautia and acetate, and breast cancer female patients with depression display lower abundances of acetate, decreased numbers of tumor-infiltrating CD8+ T cells, and an increased risk of metastasis. These results suggest that Blautia-derived acetate plays a crucial role in modulating the immune response to breast cancer, and its reduction may contribute to chronic stress-promoted cancer progression. Our findings advance the understanding of microbial and metabolic signals implicated in cancer in patients with depression and may provide therapeutic options for female patients with breast cancer and depression.
Structural insights into the conformational changes of BTR1/SLC4A11 in complex with PIP2
Authors: Lu Yishuo , Zuo Peng , Chen Hongyi , Shan Hui , Wang Weize , Dai Zonglin , Xu He , Chen Yayu , Liang Ling , Ding Dian , Jin Yan , Yin Yuxin
Published: October 2023

BTR1 (SLC4A11) is a NH3 stimulated H+ (OH-) transporter belonging to the SLC4 family. Dysfunction of BTR1 leads to diseases such as congenital hereditary endothelial dystrophy (CHED) and Fuchs endothelial corneal dystrophy (FECD). However, the mechanistic basis of BTR1 activation by alkaline pH, transport activity regulation and pathogenic mutations remains elusive. Here, we present cryo-EM structures of human BTR1 in the outward-facing state in complex with its activating ligands PIP2 and the inward-facing state with the pathogenic R125H mutation. We reveal that PIP2 binds at the interface between the transmembrane domain and the N-terminal cytosolic domain of BTR1. Disruption of either the PIP2 binding site or protonation of PIP2 phosphate groups by acidic pH can transform BTR1 into an inward-facing conformation. Our results provide insights into the mechanisms of how the transport activity and conformation changes of BTR1 are regulated by PIP2 binding and interaction of TMD and NTD.
Whole genome sequencing of increased number of azithromycin-resistant Shigella flexneri 1b isolates in Ontario
Authors: Neemuchwala Alefiya , Zittermann Sandra , Johnson Karen , Middleton Dean , Stapleton Patrick J. , Ravirajan Vithusha , Cronin Kirby , Allen Vanessa G. , Patel Samir.N.
Published: October 2023

Azithromycin (AZM) resistance among Shigella is a major public health concern. Here, we investigated the epidemiology of Shigella flexneri serotype 1b recovered during 2016–2018 in Ontario, to describe the prevalence and spread of AZM resistance. We found that 72.3% (47/65) of cases were AZM–resistant (AZMR), of which 95.7% (45/47) were among males (P < 0.001). Whole-genome based phylogenetic analysis showed three major clusters, and 56.9% of isolates grouped within a single closely-related cluster (0–10 ∆SNP). A single AZMR clonal population was persistent over 3 years and involved 67.9% (36/53) of all male cases, and none reported international travel. In 2018, a different AZMR cluster appeared among adult males not reporting travel. A proportion of isolates (10.7%) with reduced susceptibility to ciprofloxacin (CIP) due to S83L mutation in gyrA were AZM susceptible, and 71.4% reported international travel. Resistance to AZM was due to the acquisition of mph gene-bearing incFII plasmids having > 95% nucleotide similarity to pKSR100. Plasmid-borne resistance limiting treatment options to AZM, ceftriaxone (CRO) and CIP was noted in a single isolate. We characterized AZMR isolates circulating locally among males and found that genomic analysis can support targeted prevention and mitigation strategies against antimicrobial-resistance.
The effect of unisensory and multisensory information on lexical decision and free recall in young and older adults
Authors: Atkin Christopher , Stacey Jemaine E. , Roberts Katherine L. , Allen Harriet A. , Henshaw Helen , Badham Stephen P.
Published: October 2023

Studies using simple low-level stimuli show that multisensory stimuli lead to greater improvements in processing speed for older adults than young adults. However, there is insufficient evidence to explain how these benefits influence performance for more complex processes such as judgement and memory tasks. This study examined how presenting stimuli in multiple sensory modalities (audio–visual) instead of one (audio-only or visual-only) may help older adults to improve their memory and cognitive processing compared to young adults. Young and older adults completed lexical decision (real word vs. pseudoword judgement) and word recall tasks, either independently, or in combination (dual-task), with and without perceptual noise. Older adults were better able to remember words when encoding independently. In contrast, young adults were better able to remember words when encoding in combination with lexical decisions. Both young and older adults had better word recall in the audio–visual condition compared with the audio-only condition. The findings indicate significant age differences when dealing with multiple tasks during encoding. Crucially, there is no greater multisensory benefit for older adults compared to young adults in more complex processes, rather multisensory stimuli can be useful in enhancing cognitive performance for both young and older adults.
Humans inherit artificial intelligence biases
Authors: Vicente Lucía , Matute Helena
Published: October 2023

Artificial intelligence recommendations are sometimes erroneous and biased. In our research, we hypothesized that people who perform a (simulated) medical diagnostic task assisted by a biased AI system will reproduce the model's bias in their own decisions, even when they move to a context without AI support. In three experiments, participants completed a medical-themed classification task with or without the help of a biased AI system. The biased recommendations by the AI influenced participants' decisions. Moreover, when those participants, assisted by the AI, moved on to perform the task without assistance, they made the same errors as the AI had made during the previous phase. Thus, participants' responses mimicked AI bias even when the AI was no longer making suggestions. These results provide evidence of human inheritance of AI bias.
Mandibular morphology and the Mesolithic–Neolithic transition in Westernmost Iberia
Authors: Godinho Ricardo Miguel , Umbelino Cláudia , Valera António Carlos , Carvalho António Faustino , Bicho Nuno , Cascalheira João , Gonçalves Célia , Smith Patricia
Published: October 2023

Neolithic farming and animal husbandry were first developed in the Near East ~ 10,000 BCE and expanded westwards, reaching westernmost Iberia no later than 5500 BCE. It resulted in major social, cultural, economic and dietary changes. Yet, the impact of this change on human mandibular morphology in Iberia is yet to be assessed, which is regrettable because mandible form is impacted by population history and diet. In this study we used Mesolithic to Chalcolithic Iberian samples to examine the impact of this transition on mandibular morphology. We also compared these samples with a Southern Levantine Chalcolithic population to assess their relationship. Lastly, we assessed dental wear to determine if the morphological differences identified were related to the material properties of the diet. We found differences between samples in mandibular shape but not size, which we attribute to contrasting population histories between Mesolithic and later populations. Some differences in the severity of dental wear were also found between Mesolithic and later Iberian samples, and smaller between the Mesolithic Iberians and southern Levantines. Little relationship was found between wear magnitude and mandibular shape. Altogether, our results show that the Mesolithic–Neolithic Iberian transition resulted in a meaningful change in mandibular morphology, which was likely driven more by population history than by dietary change.
New horizons in the reproductive biology of Chinese pangolin (Manis pentadactyla) using the gonadal hormonal profile
Authors: Arora Bharti , Pei Kurtis Jai-Chyi , Chin Shih-Chien
Published: October 2023

The reproductive uniqueness of pangolins has been documented through diverse biological reports with discernible data discrepancies in gestation, copulation, and pregnancy. These mechanistic reproductive differences have yet to be endocrinologically quantified, which could assist in optimizing natural breeding in zoos to recover endangered species. The present research characterizes the Chinese pangolin's annual seasonal reproductive pattern by measuring immunoreactive estrogens and progestagens in 34 captive females and testosterone in 29 captive males. Our results showed that Chinese pangolins are seasonal breeders, with most births witnessed during Sept–Dec, overlapping with the field records. Females exhibited spontaneous ovulation and post-partum ovulation. Pregnant females exhibited a higher P4 level for ~ 9 months (Jan–Sept) and decreased before parturition (Oct–Dec). The circulating E2 is maintained at the baseline in pregnant females year-round. Contrastingly, in non-pregnant females, P4 is maintained at the baseline, apart from a slight elevation in January, and E2 demonstrates a sudden hike from November and remains elevated until February, suggesting the onset of ovulation. The serum testosterone concentration in males peaked during October, which is in sync with the female ovulation period. As a result that their major reproductive events, ovulation, mating, and parturition, all transpire in November-March. Evidence also supports that Chinese pangolins exhibit signs of postimplantation (pregnancy) ranging only from 5 to 6 months (May–Oct), preceded by possible facultative delay implantation triggered by lactation. The provided data not only fill in the knowledge gap for this critically endangered species but can also assist in making informed decisions, which can directly affect the successful breeding of this species in captivity.
Comparing ChatGPT and GPT-4 performance in USMLE soft skill assessments
Authors: Brin Dana , Sorin Vera , Vaid Akhil , Soroush Ali , Glicksberg Benjamin S. , Charney Alexander W. , Nadkarni Girish , Klang Eyal
Published: October 2023

The United States Medical Licensing Examination (USMLE) has been a subject of performance study for artificial intelligence (AI) models. However, their performance on questions involving USMLE soft skills remains unexplored. This study aimed to evaluate ChatGPT and GPT-4 on USMLE questions involving communication skills, ethics, empathy, and professionalism. We used 80 USMLE-style questions involving soft skills, taken from the USMLE website and the AMBOSS question bank. A follow-up query was used to assess the models’ consistency. The performance of the AI models was compared to that of previous AMBOSS users. GPT-4 outperformed ChatGPT, correctly answering 90% compared to ChatGPT’s 62.5%. GPT-4 showed more confidence, not revising any responses, while ChatGPT modified its original answers 82.5% of the time. The performance of GPT-4 was higher than that of AMBOSS's past users. Both AI models, notably GPT-4, showed capacity for empathy, indicating AI's potential to meet the complex interpersonal, ethical, and professional demands intrinsic to the practice of medicine.
The ascending limb of the cocaine unit dose–response function in rats as an experimental artifact
Authors: Desai Jhanvi N. , Tron Esqueda Luis E. , Norman Andrew B.
Published: October 2023

The cocaine unit dose–response function is an inverted U with the ascending and descending limbs representing the positive and rate limiting cocaine effects, respectively. Higher fixed ratio (FR) schedules and/or time-out periods make the ascending limb more prominent. Alternatively, a pharmacokinetic/pharmacodynamic interaction theory demonstrates that cocaine-induced lever pressing occurs only when cocaine levels are within a range termed the compulsion zone. The inter-injection intervals of self-administration increase with cocaine unit dose because of the longer time required to eliminate higher doses. However, this theory has not been applied to high FR schedules. Rats acquired cocaine self-administration on a FR1 schedule and then were changed to sessions that started with both FR1 and then FR50 over a range of unit doses with a set number of self-administrations allowed for each dose. On FR1, rats completed the maximum number of injections at all but the lowest unit dose. In contrast, on FR50 the proportion of the permitted injections increased as a function of unit dose. However, this ascending limb was the result of averaging data from sessions where rats completed or failed to complete the allowed number of injections. Rats completed all injections when cocaine levels were maintained in the compulsion zone. The FR50 schedule and low unit doses decreased this probability of maintaining cocaine levels in the compulsion zone when the rate of cocaine elimination exceeded the rate of cocaine input during the time required to complete the 50 presses. It is concluded that the ascending limb is an experimental artifact and that the entire dose–response function and the FR50-induced increase in inter-injection intervals are explained in terms of the compulsion zone theory of cocaine self-administration behavior.
Genotypic peculiarities of a human brucellosis case caused by Brucella suis biovar 5
Authors: Brangsch Hanka , Horstkotte Matthias A. , Melzer Falk
Published: October 2023

Human brucellosis cases are rare in non-endemic countries, such as Germany, where infections are predominantly caused by Brucella melitensis. The German National Reference Laboratory for Bovine, Porcine, Ovine and Caprine Brucellosis received a suspected Brucella sp. isolate from a patient for identification. Bacteriological tests and PCR-based diagnostics showed the isolate to be B. suis, but did not yield cohesive results regarding the biovar. Whole genome sequencing and subsequent genotyping was employed for a detailed characterization of the isolate and elucidating the reason for failure of the diagnostic PCR to correctly identify the biovar. The isolate was found to be B. suis bv. 5, a rare biovar with limited geographical distribution primarily found in the Northern Caucasus. Due to a deletion in one of the target regions of the diagnostic PCR, the isolate could not be correctly typed. Based on in silico genotyping it could be excluded that the isolate was identical to one of the B. suis bv. 5 reference strains. Here, we report a rare case of a B. suis bv. 5 field isolate. Furthermore, by reporting this finding, we want to make practitioners aware of possible misinterpretation of PCR results, as it cannot be excluded that the detected deletion is common among the B. suis bv. 5 community, as there is currently a lack of field isolates.
Impact of COVID-19 on TB diagnostic services at primary healthcare clinics in eThekwini district, South Africa
Authors: Dlangalala Thobeka , Musekiwa Alfred , Mashamba-Thompson Tivani
Published: October 2023

We assessed the impact of the pandemic on TB diagnostics at primary healthcare clinics (PHCs) during the different stages of COVID-19 in eThekwini district, South Africa. Data from the District Health Information System (DHIS) were used to conduct an interrupted time series analysis that assessed the changes in TB investigations and confirmed TB cases during four pandemic periods: lockdown and the subsequent three peaks of infection compared to the two years prior (2018–2022). The initial lockdown resulted in − 45% (95% CI − 55 to − 31) and − 40% (95% CI − 59 to − 28) immediate declines in TB investigations and confirmed cases, respectively. Both indicators showed substantial recovery in the months after the first wave (p < 0.05). However, while TB investigations sustained smaller declines throughout the pandemic, they rebounded and surpassed pre-COVID-19 levels by the end of the investigation period. On the other hand, confirmed cases experienced reductions that persisted until the end of the investigation period. TB diagnostic services at PHCs were considerably disrupted by COVID-19, with the confirmation of cases being the most adversely affected throughout the pandemic. The reasons for these persistent declines in TB detection must be determined to inform the development of sustainable diagnostic systems that are capable of withstanding future pandemics.
Interacting locally, acting globally: trust and proximity in social networks for the development of energy communities
Authors: Caferra Rocco , Colasante Annarita , D’Adamo Idiano , Morone Andrea , Morone Piergiuseppe
Published: October 2023

In this article, we analyze the role of social capital in the formation of sustainable energy communities. Specifically, we study the impact of different dimensions of social capital (i.e., structural, relational, cognitive) in determining willingness to participate in an energy community. Our survey data suggest that social contexts contribute to the development of energy communities, via (at least) two channels: (i) a family path, with individual perspectives showing a partial correlation with those of at least one relative, and (ii) a social channel, with higher social trust and greater interaction with neighbors favoring the propensity to participate in an energy community. The social coordination required for the formation of sustainable energy communities is determined by the quality of social interactions, and the spread of virtuous behavior is determined by not only economic policies (i.e., incentives), but also forward-looking policies favoring local aggregation and the creation of high-quality social capital. Thus, local actions and interactions can contribute to solving global climate change challenges.
State-dependent modulation of low-threshold-current-regulated dendritic Ca2+ response in thalamic reticular neurons with extracellular electric fields
Authors: Fan Yaqin , Wei Xile , Lu Meili , Wang Jiang , Yi Guosheng
Published: October 2023

Deep brain stimulation (DBS) in thalamic reticular nucleus (TRN) neuron provides a novel treatment for drug-resistant epilepsy via the induced electrical field (EFs). However, the mechanisms underlying EF effects remain unclear. This paper investigated how EFs regulate low-threshold dendritic Ca2+ (dCa) response and thus contribute to the input–output relationship of TRN cell. Our results showed that EFs modulate firing modes differently in a neuronal state-dependent manner. At the depolarized state, EFs only regulate the spike timing of a somatic stimulus-evoked single action potential (AP) with less contribution in the regulation of dCa response but could induce the transition between a dendritic stimulus-evoked single AP and a tonic burst of APs via the moderate regulation of dCa response. At the hyperpolarized state, EFs have significant effects on the dCa response, which modulate the large dCa response-dependent burst discharge and even cause a transition from this type of burst discharge to a single AP with less dCa response. Moreover, EF effects on stimulation threshold of somatic spiking prominently depend on EF-regulated dCa responses and the onset time differences between the stimulus and EF give rise to the distinct effect in the EF regulation of dCa responses. Finally, the larger neuronal axial resistance tends to result in the dendritic stimulus-evoked dCa response independent of somatic state. Interestingly, in this case, the EF application could reproduce the similar somatic state-dependent dCa response to dendritic stimulus which occurs in the case of lower axial resistance. These results suggest that the influence of EF on neuronal activities depends on neuronal intrinsic properties, which provides insight into understanding how DBS in TRN neuron modulates epilepsy from the point of view of biophysics.
Time fractional Yang–Abdel–Cattani derivative in generalized MHD Casson fluid flow with heat source and chemical reaction
Authors: Sehra  , Sadia Haleema , Haq Sami Ul , Khan Ilyas
Published: October 2023

This present research article investigates the exact analytical solution for the mathematical model of the generalized Casson fluid flow by using the new fractional operator with Rabotnov exponential kernel i.e. Yang–Abdel–Cattani operator. The impacts of heat source, magnetic hydrodynamics and chemical reactions on the flow of fractional Casson fluid through a vertical flat plate are studied in this article. For the sake of a better interpretation of the rheological behavior of Casson fluid we have used the new operator of fractional order with exponential kernel of Rabotnov known as Yang–Abdel–Cattani operator of fractional derivative. By making use of the technique of Laplace transform we have find the exact analytical solution of the problem in the Mittag–Leffler’s form, for all the three governing equations i.e. Velocity, energy and concentration equation. It has been noticed from the literature that it is challenging to obtain analytical results from fractional fluid model derived by the various fractional operators. This article helps to address this issue by providing analytical solutions for fractionalized fluid models. To analyze the physical importance of different fluid parameters such as Schmidt number, Prandtl number, MHD and alpha on the heat, mass and momentum class are presented through graphs. The concentration of the fluid decreases with Schmidth number and temperature of the fluid decreases with the increasing Prandtl number. The velocity of the fluid decreases with increasing MHD effects and increases with increasing Alpha. The Yang–Abdel–Cattani operator of fractional order can describe the memory effects more suitably than the other fractional operators.