bluuebunny/crossref_metadata_2025 huggingface dataset:
Survey of clinical microbiology and infectious disease testing capabilities among institutions in Africa
Authors: Jacobs Jeremy W , Adkins Brian D , Milner Danny A , Bloch Evan M , Eichbaum Quentin
Published: November 2024

Objectives

Inadequate laboratory infrastructure and testing capabilities are a major impediment to addressing the infectious disease burden in Africa. Therefore, the aims of this study were to characterize the clinical microbiology/infectious disease laboratory capabilities among countries in Africa.

Methods

A survey to assess the microbiological testing capabilities at hospitals, government laboratories, and free-standing public and private laboratories in African countries was developed by subject matter experts. Questions included institutional demographics and microbiology services in the broad categories of bacteriology, virology, mycology, parasitology, and rapid diagnostics/point-of-care testing. The survey was distributed using the American Society of Clinical Pathology email listserv between June and August 2022.

Results

In total, 131 unique institutions in 28 countries endorsed at least 1 type of microbiology service, with parasitology (80.9%, 106/131) and bacteriology (77.9%, 102/131) being most common, while mycology (45.0%, 59/131) and virology (45.8%, 60/131) laboratories were less prevalent. The most frequently performed bacteriology test was bacterial identification (90.2%, 92/102), followed by aerobic bacterial cultures and antimicrobial susceptibility testing (both 89.2%, 91/102). Among all clinical microbiology/infectious disease laboratories, the most commonly tested agents were HIV (90.8%, 119/131), Treponema pallidum (78.6%, 103/131), Plasmodium falciparum (76.3%, 100/131), Mycobacterium tuberculosis (76.3%, 100/131), and hepatitis C virus (74.8%, 98/131).

Conclusions

These findings provide contemporary data regarding the availability of critical infectious disease testing capabilities among institutions in Africa. These results and future additional studies will be crucial for understanding where strategic investment in the laboratory and public health infrastructure is warranted.
An intervention study on the influence of altruistic teaching on L2 learners’ English research article abstract writing
Authors: Zare Javad , Derakhshan Ali
Published: November 2024

A large mass of research has reported the significance and power of positive psychology (PP) constructs in second/foreign language (L2) education. As an offshoot of PP, altruistic teaching, which highlights teaching without self-focus, has recently initiated its way into L2 research territory. However, the way altruistic teaching influences L2 students’ academic literacy skills, such as abstract writing, has been left uncharted to date. To bridge this gap, the present study used an experimental design to investigate the contribution of altruistic teaching to 163 university students’ English abstract writing required in research article (RA)s. The results of t-test and ANOVA indicated a statistically significant difference between the learners’ RA abstract writing in the control and experimental groups in both the short and long run in light of altruistic teaching. The study discusses the results and presents the implications of altruistic teaching for L2 research and practice.
Achievement emotions in online language learning: domain-specific components and interactions with self-regulation strategies and language performance
Authors: Teng Lin Sophie , Pan Jinyun
Published: November 2024

Although previous research has underscored the crucial impact of discrete emotions on language learning, scant attention has been given to exploring domain-specific multiple achievement emotions experienced by second/foreign language (L2) learners in digital learning environments. This study aims to bridge the gap by validating a questionnaire to measure multiple achievement emotions experienced by Chinese English as a foreign language (EFL) learners during synchronous online English learning. One primary goal is to investigate the factorial structure and cultural sensitivity of achievement emotions in online English learning. This study further examines the interactions of achievement emotions with self-regulated learning (SRL) strategies and English performance to validate the criterion validity. Data were collected from 371 Chinese EFL students with intermediate to upper-intermediate L2 proficiency. Robust statistical methods, including confirmatory factor analysis and exploratory structural equation modeling (ESEM), were employed to elucidate the internal structure of achievement emotions. Model comparisons confirmed a seven-factor, correlated ESEM model comprising enjoyment, hope, pride, anger, shame-related anxiety, hopelessness, and boredom. Moderate correlations between achievement emotions and SRL strategies highlighted the interconnectedness of cognitive and emotional variables in L2 learning. Notably, this study revealed significant predictive effects of positive activating emotion (i.e. hope) and negative demotivating emotions (i.e. hopelessness and boredom) on English performance. This study concludes that the internal structure of multiple achievement emotions in online learning is embedded with situation-specific and culture-sensitivity characteristics. Moreover, the findings lend empirical support to the control-value theory, which holds that different achievement emotions have a joint and synergistic function in affecting learners’ SRL and academic performance.
Anti-inflammatory diterpenoids from the brown alga Dictyota coriacea
Authors: Shiiba Nozomi , Kumagai Momochika , Endo Hikaru , Tsuruta Tomoki , Nishikawa Keisuke , Morimoto Yoshiki
Published: November 2024

A new xenicane diterpene named 4α-acetoxyisodictyohemiacetal (1) was isolated from the brown alga Dictyota coriacea, along with 11 known diterpenoids. The structure of 1 was established by spectroscopic analyses, and its absolute configuration was determined by comparing the experimental and theoretical electronic circular dichroism spectra. Two dictyodiacetal diastereomers (5 and 6) were isolated, and the full NMR assignments were performed. The anti-inflammatory activities of the isolated compounds were evaluated using the lipopolysaccharide-stimulated mouse macrophage cell line, RAW264. The hemiacetal-containing xenicanes and dictyol-type diterpene inhibited not only the production of nitric oxide but also the expression of inducible nitric oxide synthase, interleukin-6, and cyclooxygenase-2 mRNA in RAW264 cells. This study demonstrated that diterpenes from D. coriacea may be useful as natural anti-inflammatory agents.
Delineating genomic features for wild guanaco conservation
Authors: Leggieri Leonardo Ramón , Anello Melina , Peralta Diego , Túnez Juan Ignacio , Di Rocco Florencia , Poljak Sebastián , Flores Celina , Alunni Daniela , Belardi Juan Bautista , Gutiérrez María A , Álvarez María C , Massigoge Agustina , Kaufmann Cristian , Borrero Luis , Borghi Carlos , Demartini Julieta , Petracci Pablo , Martín Sotelo , Marbán Leandro , Kathiravan Periasamy , Rudolf Pichler , Marín Juan Carlos , Cárcamo Juan Guillermo , Carmanchahi Pablo
Published: November 2024

The South American fauna has endured challenges such as illegal hunting, cattle expansion, climate change, and landscape fragmentation. Despite ongoing conservation efforts that aim to address these issues, genetic diversity remains overlooked. We genotyped 126 Lama guanicoe individuals from an area of 2 million km2 in Patagonia and Cuyo using the 60K SNPs Axiom-Camelids, and we assessed population viability through genetic diversity, inbreeding, and population size. We then explored population connectivities through network analyses, genetic differentiation, and Bayesian approaches. Our findings reveal six genetic clusters: Cuyo, Somuncura, North Patagonia, Central Patagonia, South Patagonia, and Tierra del Fuego Island (TDFI). Cuyo and TDFI guanacos differed from others due to isolation-by-distance and geographical barriers, respectively. Cuyo exhibited the highest degree of allele conservation, but TDFI faced heightened vulnerability due to isolation and increased homozygosity. Sharp bottlenecks in Cuyo and North Patagonia coincided with the expansion of sheep farming, while bottlenecks in the other populations occurred during the Little Ice Age. North Patagonia acted as a probable contact zone, facilitating mixing of the Cuyo, Somuncura, and Central Patagonia populations. The Central and South Patagonian populations presented the highest gene flow. Thus, genomic advances help to define distinct conservation units (genetic stocks) to guide management practices and decisions.
Robust model averaging approach by Mallows-type criterion
Authors: Wang Miaomiao , You Kang , Zhu Lixing , Zou Guohua
Published: November 2024

Model averaging is an important tool for treating uncertainty from model selection process and fusing information from different models, and has been widely used in various fields. However, the most existing model averaging criteria are proposed based on the methods of ordinary least squares or maximum likelihood, which possess high sensitivity to outliers or violation of certain model assumption. For the mean regression, no optimal robust methods are developed. To fill this gap, in our paper, we propose an outlier-robust model averaging approach by Mallows-type criterion. The idea is that we first construct a generalized M (GM) estimator for each candidate model, and then build robust weighting schemes by the asymptotic expansion of the final prediction error based on the GM-type loss function. So, we can still achieve a trustworthy result even if the dataset is contaminated by outliers in response and/or covariates. Asymptotic properties of the proposed robust model averaging estimators are established under some regularity conditions. The consistency of our weight estimators tending to the theoretically optimal weight vectors is also derived. We prove that our model averaging estimator is robust in terms of having bounded influence function. Further, we define the empirical prediction influence function to evaluate the quantitative robustness of the model averaging estimator. A simulation study and a real data analysis are conducted to demonstrate the finite sample performance of our estimators and compare them with other commonly used model selection and averaging methods.
Multicentre analysis of seizure outcome predicted by removal of high frequency oscillations
Authors: Dimakopoulos Vasileios , Gotman Jean , Klimes Petr , von Ellenrieder Nicolas , Tan Shi Bei , Smith Garnett , Gliske Stephen , Maltseva Margarita , Manalo Minette Krisel , Pail Martin , Brazdil Milan , van Blooijs Dorien , van ‘t Klooster Maryse , Johnson Sarah , Laboy Samantha , Ledergerber Debora , Imbach Lukas , Papadelis Christos , Sperling Michael R , Zijlmans Maeike , Cimbalnik Jan , Jacobs Julia , Stacey William C , Frauscher Birgit , Sarnthein Johannes
Published: November 2024

In drug-resistant focal epilepsy, planning surgical resection may involve presurgical intracranial EEG recordings (iEEG) to detect seizures and other iEEG patterns to improve postsurgical seizure outcome. We hypothesized that resection of tissue generating interictal high frequency oscillations (HFOs, 80-500 Hz) in the iEEG predicts surgical outcome.

Eight international epilepsy centres recorded iEEG during the patients’ pre-surgical evaluation. The patients were of all ages, had epilepsy of all types, and underwent surgical resection of a single focus aiming at seizure freedom. In a prospective analysis we applied a fully automated definition of HFO which was independent of the dataset. Using an observational cohort design that was blinded to postsurgical seizure outcome, we analysed HFO rates during non-rapid-eye-movement sleep. If channels had consistently high rates over multiple epochs, they were labelled the “HFO area”. After HFO analysis, centres provided the electrode contacts located in the resected volume and the seizure outcome at follow-up ≥24 months after surgery. The study was registered at www.clinicaltrials.gov (NCT05332990).

We received 160 iEEG datasets. In 146 datasets (91%), the HFO area could be defined. The patients with completely resected HFO area were more likely to achieve seizure freedom compared to those without (OR 2.61 CI [1.15-5.91], P = 0.02). Among seizure free patients, the HFO area was completely resected in 31 and was not completely resected in 43. Among patients with recurrent seizures, the HFO area was completely resected in 14 and was not completely resected in 58. When predicting seizure freedom, the negative predictive value of the HFO area (68% CI [52-81]) was higher than that for the resected volume as predictor by itself (51% CI [42-59], P = 4e-5). The sensitivity and specificity for complete HFO area resection were 0.88 CI [0.72-0.98] and 0.39 CI [0.25-0.54] and the area under the curve was 0.83 CI [0.58-0.97], indicating good predictive performance.

In a blinded cohort study from independent epilepsy centres, applying a previously validated algorithm for HFO marking without the need of adjusting to new datasets allowed us to validate the clinical relevance of HFOs to plan the surgical resection.
Current state and perspectives of CAR T cell therapy in central nervous system diseases
Authors: Pfeffer Lena Kristina , Fischbach Felix , Heesen Christoph , Friese Manuel A
Published: November 2024

B cell-directed CAR T cell therapy has fundamentally changed the treatment of haematological malignancies, and its scope of application is rapidly expanding to include other diseases such as solid tumours or autoimmune disorders. Therapy-refractoriness remains an important challenge in various inflammatory and non-inflammatory disorders of the CNS. The reasons for therapy failure are diverse and include the limited access current therapies have to the CNS, as well as enormous inter- and intra-individual disease heterogeneity. The tissue-penetrating properties of CAR T cells make them a promising option for overcoming this problem and tackling pathologies directly within the CNS.

First application of B cell-directed CAR T cells in neuromyelitis optica spectrum disorder and multiple sclerosis patients has recently revealed promising outcomes, expanding the potential of CAR T cell therapy to encompass CNS diseases. Additionally, the optimization of CAR T cells for the therapy of gliomas is a growing field. As a further prospect, preclinical data reveal the potential benefits of CAR T cell therapy in the treatment of primary neurodegenerative diseases such as Alzheimer’s disease.

Considering the biotechnological optimizations in the field of T cell engineering, such as extension to target different antigens or variation of the modified T cell subtype, new and promising fields of CAR T cell application are rapidly opening up. These innovations offer the potential to address the complex pathophysiological properties of CNS diseases. To use CAR T cell therapy optimally to treat CNS diseases in the future while minimizing therapy risks, further mechanistic research and prospective controlled trials are needed to assess seriously the disease and patient-specific risk-benefit ratio.
Solvent-free catalytic synthesis of ureas from amines and carbon dioxide under atmospheric pressure using oxovanadium(V) catalyst with silylating reagent
Authors: Aoyama Kotaro , Tsuda Moeka , Shigematsu Hiroto , Moriuchi Toshiyuki
Published: November 2024

Efficient utilization of carbon dioxide for the synthesis of valuable compounds is considered to be essential for the future sustainable society. Herein, N,O-bis(trimethylsilyl)acetamide, which acts not only as a silylating reagent but also as a reaction solvent, was demonstrated to facilitate the solvent-free catalytic synthesis of ureas in 1-step from amines and carbon dioxide under atmospheric pressure using a commercially available air-stable NH4VO3 catalyst. This catalytic system was applicable to a wide range of substrate and a gram-scale reaction. One-step preferential synthesis of unsymmetrical ureas was also realized.
Reverse symbolic action and quiescence: a critical exploration of anti-abortion rhetoric and movement activation
Authors: Marquess Mackenzie O
Published: November 2024

Following the Dobbs v. Jackson Women’s Health Organization Supreme Court decision, the pro-choice movement had a clear spike in motivation and action. The Republican Party hosted a celebratory news conference following the decision, but rather than activating their own base they witnessed an unintentional activation of their opposing base. This article proposes a theory of reverse symbolic action which explores the possibility that extreme anti-abortion rhetoric caused the pro-life movement to fall into dormancy while causing the pro-choice movement to activate. Drawing on social judgment theory and politics as symbolic action, reverse symbolic action has three dimensions: policy action producing quiescence, rhetorical overreach, and unintentional activation of the oppositional base. A case study applies this new theoretical lens to the House Republican news conference held immediately after the announcement of Dobbs. Public responses are explored through analysis of Twitter activity following the conference and the 2022 midterm election results.
Microvascular resistance reserve in relation to total and vessel-specific atherosclerotic burden
Authors: Hoshino Masahiro , Jukema Ruurt A , Hoek Roel , Dahdal Jorge , Raijmakers Pieter , Driessen Roel , Bom Michiel J , van Diemen Pepijn , Twisk Jos , Danad Ibrahim , Kakuta Tsunekazu , Knuuti Juhani , Knaapen Paul
Published: November 2024

Aims

The relationship between coronary artery atherosclerosis and microvascular resistance remains unclear. This study aims to clarify the relationship between total atherosclerotic and vessel-specific atherosclerotic burden and microvascular resistance reserve (MRR).

Methods and results

In this post hoc analysis of the PACIFIC 1 trial, symptomatic patients without prior coronary artery disease (CAD) underwent [15O]H2O positron emission tomography, coronary computed tomography angiography (CCTA), and invasive fractional flow reserve (FFR). MRR was assessed across all three coronary branches, utilizing PET-derived coronary flow reserve and invasive FFR measurements. CCTA was used to assess patient and vessel-specific plaque volumes. Percentage atheroma volume (PAV) was defined as total plaque volume divided by vessel volume. The study included 142 patients (55% male, 57.5 ± 8.6 years) with 426 vessels with a mean MRR of 3.77 ± 1.64. While a significantly higher PAV was observed in the left anterior descending artery territory, MRR was similar across the three coronary branches. Generalized estimating equations without correction for cardiovascular risk factors identified that patient-specific PAV tertiles but not vessel-specific PAV tertiles were related to vessel-specific MRR. After correction for cardiovascular risk factors, compared with the first tertile of patient-specific PAV, the second tertile showed a vessel-specific MRR decrease of β = −0.362, P = 0.018, and the third tertile showed a decrease of β = −0.347, P = 0.024.

Conclusion

In patients without prior CAD, patient-specific plaque burden was negatively associated to vessel-specific MRR; however, vessel-specific plaque burden was not related to vessel-specific MRR. Our findings suggest that the relation between atherosclerotic burden and an impaired microcirculatory function is of systemic origin.
Thoracic posture-related morphological changes in patients with pectus excavatum versus healthy controls
Authors: Suzuki Takahiro , Asakura Keisuke , Yamada Yoshitake , Masai Kyohei , Yamada Minoru , Yokoyama Yoichi , Okubo Yu , Kaseda Kaoru , Hishida Tomoyuki , Jinzaki Masahiro
Published: November 2024

OBJECTIVES

Cases of severe pectus excavatum presenting with worsening cardiopulmonary symptoms in the upright position have been reported. However, the underlying mechanism remains unclear. We evaluated posture-related morphological changes of the thorax in patients with pectus excavatum.

METHODS

Chest morphology was evaluated preoperatively using upright and supine computed tomography in 21 patients with pectus excavatum and 35 healthy volunteers. The minimum anterior–posterior thoracic diameter, depression depth, and Haller index on horizontal sections, as well as the T6-12 plumb line distance on sagittal sections, were compared between the 2 positions.

RESULTS

In patients with pectus excavatum (median age, 22 years; 18 males and 3 females), the minimum anterior–posterior diameter was smaller (4.5 vs 5.1 cm, P < 0.001) and the Haller index was greater (10.1 vs 6.4, P < 0.001) in the upright position than in the supine position. The T6-T12 plumb line distance was longer in the upright position (2.4 vs 0.8 cm, P < 0.001), while the depression depth showed no significant difference. Healthy volunteers exhibited similar changes. The degree of spinal curvature increased in the upright position due to the anterior shift of the lower thoracic vertebrae, resulting in a shorter anterior–posterior diameter, irrespective of chest wall deformity. One patient with dyspnoea only in the upright position exhibited compression of the right inferior pulmonary vein only on upright computed tomography.

CONCLUSIONS

The minimum anterior–posterior diameter is shorter in the upright position. This may explain the worsening of cardiopulmonary symptoms in patients with severe pectus excavatum when in an upright position.

Clinical trial registration number: UMIN000036438

https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000041519
General practice utilisation by Australian cancer patients in the last year of life
Authors: Grant Matthew P , McCarthy Damien , Kearney Chris , Collins Anna , Sundararajan Vijaya , Rhee Joel J , Philip Jennifer A M , Emery Jon D
Published: November 2024

Objectives

General practice plays a key role in end-of-life care, yet the extent of this remains largely unknown due to a lack of detailed clinical data. This study aims to describe the care provided by General Practitioners (GPs) for people with cancer in their last year of life.

Methods

Retrospective cohort study using linked routine primary care and death certificate data in Victoria, Australia. Patients were included who died from cancer between 2008 and 2017.

Results

In total 7025 cancer patients were included, mean age of 74.8 yrs. 95% of patients visited their GP in the last 6 months of life, with a median of 11 general practice contacts in this period. 72% of patients visited their GP in the second-last month prior to death, and 74% in the last month of life. The majority of patients (58%) were prescribed opioids, 19% anticipatory medications, 24% received a home visit, and a small proportion had imaging (6%) in the last month and pathology (6%) in the last fortnight. Patients in regional areas had more contact with general practices in the last year of life compared to metropolitan patients (median metropolitan = 16, inner regional = 25, and outer regional = 23, P < .001). The use of GP services did not differ by cancer type.

Conclusions

GP’s play a central role in end-of-life care provision for cancer patients, which intensifies in the last months of life. There is room for improvement, with a proportion having little or no engagement, and low rates of home visits and anticipatory medication prescribing.
Impact of a multifaceted intervention programme on antibiotic prescribing and dispensing in four patient-centred settings in five European countries. The HAPPY PATIENT project
Authors: García-Sangenís Ana , Lykkegaard Jesper , Hansen Malene Plejdrup , González López-Valcárcel Beatriz , Raynal Fabiana , Vallejo-Torres Laura , Bjerrum Lars , Chalkidou Athina , Jensen Jette Nygaard , Rebnord Ingrid , Lindberg Bent Håkan , Taxis Katja , Lambert Maarten , Radzeviciene Ruta , Jaruseviciene Lina , Touboul Lundgren Pia , Bruno Pascale , Lesage Vanessa , Kowalczyk Anna , Godycki-Cwirko Maciej , Lionis Christos , Karkana Maria-Nefeli , Anastasaki Marilena , Hansen Matilde Bøgelund , Olsen Jonas Kanstrup , Søndergaard Jens , Modena Daniela , Mally Stella , Álvarez Laura , Llor Carl
Published: November 2024

Background

The primary cause of antimicrobial resistance is excessive and non-indicated antibiotic use.

Aim

To evaluate the impact of a multifaceted intervention aimed at various healthcare professionals (HCPs) on antibiotic prescribing and dispensing for common infections.

Design and setting

Before-and-after study set in general practice, out-of-hours services, nursing homes, and community pharmacies in France, Greece, Lithuania, Poland, and Spain.

Methods

Following the Audit Project Odense method, HCPs from these four settings self-registered encounters with patients related to antibiotic prescribing and dispensing before and after an intervention (February–April 2022 and February–April 2023). Prior to the second registration, the HCPs undertook a multifaceted intervention, which included reviewing and discussing feedback on the first registration’s results, enhancing communication skills, and providing communication tools. Indicators to identify potentially unnecessary prescriptions and non-first-line antibiotic choices were developed, and the results of the two registrations were compared.

Results

A total of 345 HCPs registered 10 744 infections in the first registration period and 10 207 infections in the second period. In general practice, participants showed a significant 9.8% reduction in unnecessary antibiotic prescriptions in the second period, whereas limited or no effect was observed in out-of-hours services and nursing homes (0.8% reduction and 4.5% increase, respectively). Pharmacies demonstrated an 18% increase in safety checks, and correct advice in pharmacies rose by 17%.

Conclusion

External factors like COVID-19, antibiotic shortages, and a streptococcal epidemic impacted the intervention’s benefits. Despite this, the intervention successfully improved antibiotic use in both settings.
Latitudinal gradients and ocean fronts strongly influence protist communities in the southern Pacific Ocean
Authors: Sturm Daniela , Morton Peter , Langer Gerald , Balch William M , Wheeler Glen
Published: November 2024

Protist communities in the southern Pacific Ocean make a major contribution to global biogeochemical cycling, but remain understudied due to their remote location. We therefore have limited understanding of how large-scale physical gradients (e.g. temperature) and mesoscale oceanographic features (e.g. fronts) influence microeukaryote diversity in this region. We performed a high-resolution examination of protist communities along a latitudinal transect (>3000 km) at 150°W in the central southern Pacific Ocean that encompassed major frontal regions, including the subtropical front (STF), the subantarctic front (SAF), and the polar front (PF). We identified distinct microbial communities along the transect that were primarily delineated by the positions of the STF and PF. Some taxa were not constricted by these environmental boundaries and were able to span frontal regions, such as the colonial haptophyte Phaeocystis. Our findings also support the presence of a latitudinal diversity gradient (LDG) of decreasing diversity of the protist community with increasing latitude, although some individual taxa, notably the diatoms, do not adhere to this rule. Our findings show that oceanographic features and large-scale physical gradients have important impacts on marine protist communities in the southern Pacific Ocean that are likely to strongly influence their response to future environmental change.
A path integral approach for allele frequency dynamics under polygenic selection
Authors: Anderson Nathan W , Kirk Lloyd , Schraiber Joshua G , Ragsdale Aaron P
Published: November 2024

Many phenotypic traits have a polygenic genetic basis, making it challenging to learn their genetic architectures and predict individual phenotypes. One promising avenue to resolve the genetic basis of complex traits is through evolve-and-resequence (E&R) experiments, in which laboratory populations are exposed to some selective pressure and trait-contributing loci are identified by extreme frequency changes over the course of the experiment. However, small laboratory populations will experience substantial random genetic drift, and it is difficult to determine whether selection played a role in a given allele frequency change (AFC). Predicting AFCs under drift and selection, even for alleles contributing to simple, monogenic traits, has remained a challenging problem. Recently, there have been efforts to apply the path integral, a method borrowed from physics, to solve this problem. So far, this approach has been limited to genic selection, and is therefore inadequate to capture the complexity of quantitative, highly polygenic traits that are commonly studied. Here, we extend one of these path integral methods, the perturbation approximation, to selection scenarios that are of interest to quantitative genetics. We derive analytic expressions for the transition probability (i.e. the probability that an allele will change in frequency from x to y in time t) of an allele contributing to a trait subject to stabilizing selection, as well as that of an allele contributing to a trait rapidly adapting to a new phenotypic optimum. We use these expressions to characterize the use of AFC to test for selection, as well as explore optimal design choices for E&R experiments to uncover the genetic architecture of polygenic traits under selection.
“It was not the will to live that drove me...”: Escapees from Treblinka Death Camp Returning to the Warsaw Ghetto
Authors: Ferenc Maria
Published: November 2024

This article examines a pivotal moment during the Holocaust among the Jews in the Warsaw ghetto—the return to Warsaw of eyewitness survivors who managed to escape from the Treblinka death camp during summer and autumn 1942. These individuals, who had personally witnessed the atrocities, were fueled by a profound sense of duty to attest to the horrors of the extermination camp, and thus they sought to inform and caution the remaining Jewish population. This article explores the dynamics of these escapees’ return and delves into the details of their testimonies, as well as how the ghetto population reacted to information about Treblinka. While many were eager to uncover the truth about the fate of the deportees, the harsh reality proved difficult to bear for many and escapees’ accounts often faced skepticism. The article also reveals that the urge to alert fellow Jews about the ongoing Holocaust heavily motivated those who fled Treblinka in this time. On a more general level, this case study broadly examines the process by which information transforms into knowledge.
4-Phenylbutyric acid mitigates ER stress-induced neurodegeneration in the spinal cords of a GM2 gangliosidosis mouse model
Authors: Weaver Fiona E , White Elizabeth , Peek Allyson M , Nurse Colin A , Austin Richard C , Igdoura Suleiman A
Published: November 2024

Sandhoff disease (SD), a fatal and rare lysosomal storage disorder (LSD), is caused by a deficiency of the enzyme β-hexosaminidase B and leads to severe accumulation of GM2 gangliosides in lysosomes, primarily within the central nervous system (CNS). This accumulation results in severe neurological impairment, lower motor neuron disease, and death. Currently, there are no effective therapies available for SD. Here, we explored the role of endoplasmic reticulum (ER) stress in the spinal cord during disease progression in an established mouse model of SD and revealed the beneficial outcome of off-label treatment with the FDA-approved drug, 4-phenylbutyric acid (4-PBA). We analyzed the expression and localization of ER stress and cellular apoptosis markers, which revealed significant upregulation of these factors within motor neurons. Additionally, we observed a > 50% reduction in neuronal numbers throughout all spinal cord regions. Our studies also tested the impact of the chemical chaperone 4-PBA on ER stress in mice, and following administration, we observed significant improvements in motor neuromuscular function and life span throughout disease progression. 4-PBA treatment significantly reduced apoptosis in spinal cord neurons and increased the number of choline acetyltransferase (ChAT)-positive neurons, with little effect on astrogliosis or sensory interneurons. Overall, this study provides strong evidence for the role of chronic ER stress in the pathophysiology of SD and highlights 4-PBA as a promising therapeutic treatment for SD and potentially other related LSDs.
Evolutionary game model for decarbonization of shipping under green shipping corridor
Authors: Zhang Suyong , Feng Chuwei
Published: November 2024

The journey of zero-emission shipping has begun. In the context of green shipping corridor, this paper constructs a three-party evolutionary game model of the government, shipping enterprises and shippers, and analyzes the stability of the game model. Based on the corresponding policy and market environments, a sensitivity analysis of the key parameters is carried out using MATLAB tools. The results show the following: (1) The tripartite strategy will eventually evolve into {government adopts active policy, shipping enterprises respond positively, consignor respond positively}. This evolutionary result is also more consistent with the reality of emission reduction under the high cost of shipping emission reduction today. (2) Government subsidies, social financing, and the increase of carbon price level can lead shipping enterprises to respond positively. (3) Attention should be paid to the idea of decarbonization driven by the demand side, and the power of all parties should be gathered to participate in the decarbonization of shipping to achieve the carbon reduction target as soon as possible.
An experimental study to lift water with a solar-driven bubble pump
Authors: Omar Ihab , Al.Bahadli Yusra A , Hussaina Zahra F , Altayeh Aiham O , Saleh Ahmed A M , Basem Ali
Published: November 2024

This study presents an experimental investigation centered on the utilization of a solar bubble pump for lifting water. Experimental tests were conducted to analyze the impact of various design and operational parameters. The results revealed a direct proportionality between the maximum height lifted heat flux. Additionally, the experiments demonstrated that increasing the submergence ratio resulted in a higher mass flow of lifted water. Furthermore, a slight increase in tube diameter, while maintaining a constant heat flux and submergence ratio, led to a 22.47% increase in the flow rate when the diameter was increased from 8 mm to 10.21 mm.
TUPE’s public–private divide: Bicknell (1) The British Medical Association (2) v NHS Nottingham and Nottinghamshire Integrated Commissioning Board
Authors: Wynn-Evans Charles
Published: November 2024

This note reviews the decision of the Employment Appeal Tribunal in Bicknell (1) The British Medical Association (2) v NHS Nottingham and Nottinghamshire Integrated Commissioning Board and its consideration of the limitation of the scope of the Transfer of Undertakings (Protection of Employment) Regulations 2006 to ‘economic activity’. This limitation, when combined with the exclusion from the application of the transfer of undertakings legislation of ‘public administrative’ reorganisations, creates a public–private divide—a ‘public sector exclusion zone’—in the application of the transfer of undertakings regime. This note argues that the doubts expressed by the EAT in Bicknell about the decision in Nicholls & Anor v London Borough of Croydon & Ors—in which it was held that the purchasing and commission of goods and services do not constitute an economic activity for the purposes of the transfer legislation—are well founded. The approach adopted in Nicholls, which was based on EU competition law authorities addressing the entirely different context of the regulation of competition, should therefore be revisited. Applying a purposive TUPE-specific approach, the purchasing and commission of goods and services should, depending on the factual matrix, be treated as capable of constituting an economic activity for the purposes of TUPE. This approach would, consistent with the objectives of the transfer legislation, enable the (better) protection of the employment of those engaged in purchasing and commissioning activities, whether or not conducted under the broad umbrella of the public sector, who are affected by reorganisations and similar exercises otherwise satisfying the requirements of a TUPE transfer.
Association of Messenger RNA Coronavirus Disease 2019 (COVID-19) Vaccination and Reductions in Post COVID Conditions Following Severe Acute Respiratory Syndrome Coronavirus 2 Infection in a US Prospective Cohort of Essential Workers
Authors: Mak Josephine , Khan Sana , Britton Amadea , Rose Spencer , Gwynn Lisa , Ellingson Katherine D , Meece Jennifer , Feldstein Leora R , Tyner Harmony , Edwards Laura J , Thiese Matthew S , Naleway Allison , Gaglani Manjusha , Solle Natasha , Burgess Jefferey L , Lamberte Julie Mayo , Shea Meghan , Hunt-Smith Taryn , Caban-Martinez Alberto , Porter Cynthia , Wiegand Ryan , Rai Ramona , Hegmann Kurt T , Hollister James , Fowlkes Ashley , Wesley Meredith , Philips Andrew L , Rivers Patrick , Bloodworth Robin , Newes-Adeyi Gabriella , Olsho Lauren E W , Yoon Sarang K , Saydah Sharon , Lutrick Karen
Published: November 2024

Background

Data are limited on whether vaccination reduces post COVID conditions (PCCs) risk after less severe nonhospitalized coronavirus disease 2019 (COVID-19). This study assessed whether COVID-19 vaccination protected against PCCs in persons with mild initial infections during Delta and Omicron variant predominance.

Methods

This study utilized a case-control design, nested within the HEROES-RECOVER cohort. Participants aged ≥18 years with test–confirmed severe acute respiratory syndrome coronavirus disease 2 (SARS-CoV-2) between 28 June 2021 and 14 September 2022 were surveyed for PCCs, defined by symptoms lasting >4 weeks after initial infection. Cases self-reported PCCs and controls self-reported no PCCs. The exposure was messenger RNA (mRNA) COVID-19 vaccination (2 or 3 monovalent doses). Odds of PCCs among vaccinated and unvaccinated persons were compared with logistic regression.

Results

Of 936 participants, 23.6% reported PCCs and 83.2% were vaccinated. Participants who received 3 vaccine doses had lower odds of PCC-related gastrointestinal, neurological, and other symptoms compared to unvaccinated participants (adjusted odds ratio [95% confidence interval]: 0.37 [.16–.85], 0.56 [.32–.97], and 0.48 [.25–.91], respectively).

Conclusions

COVID-19 vaccination protected against development of PCCs among persons with mild infection during both Delta and Omicron variant predominance, supporting vaccination as an important PCCs prevention tool.
Pathobiont and symbiont contribute to microbiota homeostasis through Malpighian tubules–gut countercurrent flow in Bactrocera dorsalis
Authors: Liu Yanning , Luo Rengang , Bai Shuai , Lemaitre Bruno , Zhang Hongyu , Li Xiaoxue
Published: November 2024

Host–gut microbiota interactions are more complex than good or bad. Both gut symbiotic bacteria and pathobionts can provide essential functions to their host in one scenario and yet be detrimental to host health in another. So, these gut-dwelling bacteria must be tightly controlled to avoid harmful effects on the host. However, how pathobionts and other symbiotic bacteria coordinate to establish a host immune defense system remains unclear. Here, using a Tephritidae fruit fly Bactrocera dorsalis, we report that both pathobionts and other gut symbiotic bacteria release tyramine, which is recognized by the host insects. These tyramines induce the formation of insect-conserved Malpighian tubules–gut countercurrent flow upon bacterial infection, which requires tyramine receptors and aquaporins. At the same time, pathobionts but not gut symbiotic bacteria induce the generation of reactive oxygen species, which are preserved by the countercurrent flow, promoting bacteria elimination through increasing gut peristalsis. More importantly, our results show that the Malpighian tubules–gut countercurrent flow maintains proper microbiota composition. Our work suggests a model where pathobiont-induced reactive oxygen species are preserved by Malpighian tubules–gut countercurrent flow involving both pathobionts and symbiotic bacteria. Furthermore, our work provides a Malpighian tubules–gut interaction that ensures efficient maintenance of the gut microbiota.
Impact of knowledge of human papillomavirus positivity on cervical cytology performance in Latin America
Authors: Ramírez Arianis Tatiana , Mesher David , Baena Armando , Salgado Yuli , Kasamatsu Elena , Cristaldo Carmen , Álvarez Rodrigo , Rojas Freddy David , Ramírez Katherine , Guyot Julieta , Henríquez Odessa , González Palma Hans , Flores Bettsy , Peñaranda Jhaquelin , Vero María José , Robinson Isabel , Rol Mary Luz , Rodríguez Guillermo , Terán Carolina , Ferrera Annabelle , Picconi María Alejandra , Calderon Alejandro , Mendoza Laura , Wiesner Carolina , Almonte Maribel , Herrero Rolando ,   ESTAMPA Study Group, Colucci María Celeste , Reynaga Daysi Colque , Fernández Daniel Llanos , Ortube Omar , Martínez Sandra , González Emmanuel , Guillén Diego , Cabrera Yessy , Mongelós Pamela , Rodríguez María Isabel , Soilán Ana , Ortega Marina , Duarte Elizabeth , García Laura , Caserta Benedicta , Darragh Teresa , Downham Laura
Published: November 2024

Background

Cervical cytology is recommended by the World Health Organization as a triage option in human papillomavirus (HPV)-based cervical cancer screening programs. We assessed the performance of cytology to detect CIN3+ without and with knowledge of HPV positivity.

Methods

Women were screened with cytology and HPV across ESTAMPA study centers in Latin America. Screen-positives were referred to colposcopy with biopsy and treatment as needed. Cytology was initially interpreted without knowing HPV results. A subset of cytologies from HPV-positive women were reinterpreted at the same laboratories, with knowledge of HPV status, blinded to previous cytology and histological diagnosis. Performance indicators for cytology to detect CIN3+ without and with knowledge of HPV positivity were estimated.

Findings

A total of 4087 women were included, of which 490 had histologically confirmed CIN3+ (455 CIN3 and 35 cancers). Cytology sensitivity without knowledge of HPV positivity for CIN3+ was 47.2% (95% CI = 42.5 to 51.9), whereas with knowledge of HPV positivity, the sensitivity was higher (58.9%, 95% CI = 54.2 to 63.5; P < .0001). The specificity without knowledge of HPV was 89.4% (95% CI = 88.2 to 90.5), whereas with knowledge of HPV positivity was 78.9% (95% CI = 77.4 to 80.4; P < .0001). Performance estimates varied by study center for cytology without knowing the HPV positivity (range = 32.8%-61.5% for sensitivity; range = 80.7%-98.6% for specificity). Similarly, performance varied with knowledge of HPV positivity (36.1%-93.4% for sensitivity; 39.6%-98.6% for specificity).

Conclusion

The increase in sensitivity of cytology with HPV knowledge was limited and highly variable, reinforcing the need for alternative triage methods to support cervical cancer elimination goals.
Impact of major depressive disorder on breast cancer outcomes: a national retrospective cohort study
Authors: Aboumrad Maya , Joshu Corinne , Visvanathan Kala
Published: November 2024

Background

Establishing whether women with major depressive disorder who develop breast cancer have poor outcomes is key to optimizing care for this population. To this end, we examined associations between major depressive disorder and breast cancer recurrence and mortality.

Methods

Using medical record data from the US Department of Veterans Affairs health-care system, we established a retrospective cohort of women with local or regional stage invasive breast cancer between 2010 and 2019 and followed them through 2022. We used a 2-year window to identify women diagnosed with major depressive disorder before breast cancer diagnosis. We used multivariable Cox-proportional hazards regression to estimate associations between major depressive disorder and breast cancer recurrence and mortality while accounting for competing risks and adjusting for sociodemographic, clinical, lifestyle, and tumor characteristics.

Results

We identified 6051 women with breast cancer, of whom 1754 (29%) had major depressive disorder. The mean (SD) age at breast cancer diagnosis was 57 (11) years. In multivariable analyses, women with major depressive disorder had a 37% (hazard ratio = 1.37, 95% CI = 1.19 to 1.57) higher risk of recurrence and a 30% (hazard ratio = 1.30, 95% CI = 1.02 to 1.64) higher risk of breast cancer mortality. The association between major depressive disorder and recurrence was stronger among women with estrogen receptor–positive breast cancer. In secondary analyses, there were statistically significant interactions between major depressive disorder and multiple exposures with respect to recurrence, including current smoking, substance abuse, and nonreceipt of screening mammography.

Conclusions

Women with major depressive disorder had inferior breast cancer outcomes compared with women without a history of major depressive disorder. Research is needed to investigate underlying mechanisms linking depression to breast cancer progression and evaluate interventions to improve outcomes in this high-risk population.
Single-dose human papillomavirus vaccination: an update
Authors: Kreimer Aimée R , Watson-Jones Deborah , Kim Jane J , Dull Peter
Published: November 2024

Human papillomavirus (HPV) vaccines received regulatory approval and were recommended for use in young girls nearly 2 decades ago. Uptake is mostly high in resource-rich settings. In resource-limited settings, where the burden of cervical cancer is disproportionately high, access to and uptake of HPV vaccines are nowhere near satisfactory, despite evidence that HPV vaccination is highly cost-effective and a significant value-for-money investment. The discovery that only a single dose of the HPV vaccines may be needed to confer adequate protection may make equitable access to HPV vaccines possible. Indeed, the recent World Health Organization recommendation allowing for 1 or 2 doses is already gaining traction. This monograph aims to update the state of the science related to single-dose HPV vaccine protection and includes both primary data and modeling efforts that address key gaps in the knowledge regarding 1) durability of protection of a single dose of the HPV vaccine, 2) single-dose HPV vaccine effectiveness in both high-income and low-income settings, 3) implementation of single-dose HPV vaccination, and 4) how to accelerate control of cervical cancer by integrating a 1-time screen for cervical disease. The content published in this monograph will continue to advance the science of HPV vaccination and will be vital as new countries make informed decisions about how best to use this remarkable vaccine.