bluuebunny/crossref_metadata_2025 huggingface dataset:
Ultra-low background germanium assay at the Boulby Underground Laboratory
Authors: Scovell P.R. , Meehan E. , Paling S.M. , Thiesse M. , Liu X. , Ghag C. , Ginsz M. , Quirin P. , Ralet D.
Published: January 2024

As we move to an era where next generation ultra-low
background particle physics experiments begin to be designed and
constructed, the ability to assay materials with high sensitivity
and at speed with a variety of techniques will be key.

This paper describes the Mirion Technologies (Canberra) specialty
ultra-low background detectors installed and commissioned at the
Boulby Underground Laboratory between 2017 and 2021. The low
background levels of the detectors combine with low background
shielding and a radon-reduced dry nitrogen purge system to give
sensitivity approaching the best in the world without the need for
intricate shielding solutions.

For an optimised sample geometry, run for 100 d, it would be
possible to reach close to 10 μBq kg-1
(10-12 g/g) for background radionuclides of interest in
neutrinoless double-beta decay.
Quantum and classical simulation of core shell based junctionless field effect transistor with digital application
Authors: Mehta Vanita , Kumar Arya Sandeep , Sharma Rajiv
Published: January 2024

The detailed performance analysis of core–shell Gate All Around junctionless field effect transistor along with CMOS inverter as an application with quantum models is presented in this paper for the first time. To appreciate the performance of the device and the application even at smaller channel length, the comparison with classical models is also presented. The OFF current was calculated as 3.68 × 10−16A on incorporating the quantum models. The subthreshold swing (SS) and Drain induced barrier lowering (DIBL) are found to be near ideal values. The SS and DIBL was calculated as 62.82 mV/dec and 33.4 mV/V. The DIBL was found to be lesser by 52.82% with quantum model than classical model. The performance obtained using quantum models are better than the classical models in terms of different parameters such as OFF current, ON current, SS, DIBL, threshold voltage, transconductance. Further, the performance of the CMOS inverter with quantum models by considering the n-type and p-type core–shell Gate All Around junctionless field effect transistor is also presented . The OFF current of p-type and n-type was matched before designing the application. A sharp transfer characteristics of the CMOS inverter is obtained. The performance was also studied by calculating the drain current from each of p-type and n-type and found to be more than 1 × 10−7A and SNM (Static Noise Margin) was calculated as 267 mV. The transient response of CMOS inverter exhibits the potential of CMOS inverter using the proposed device even at smaller channel lengths.
Dysfunctions of multiscale dynamic brain functional networks in subjective cognitive decline
Authors: Liu Mianxin , Huang Qi , Huang Lin , Ren Shuhua , Cui Liang , Zhang Han , Guan Yihui , Guo Qihao , Xie Fang , Shen Dinggang
Published: January 2024

Subjective cognitive decline is potentially the earliest symptom of Alzheimer's disease, whose objective neurological basis remains elusive. To explore the potential biomarkers for subjective cognitive decline, we developed a novel deep learning method based on multiscale dynamical brain functional networks to identify subjective cognitive declines. We retrospectively constructed an internal data set (with 112 subjective cognitive decline and 64 healthy control subjects) to develop and internally validate the deep learning model. Conventional deep learning methods based on static and dynamic brain functional networks are compared. After the model is established, we prospectively collect an external data set (26 subjective cognitive decline and 12 healthy control subjects) for testing. Meanwhile, our method provides monitoring of the transitions between normal and abnormal (subjective cognitive decline–related) dynamical functional network states. The features of abnormal dynamical functional network states are quantified by network and variability metrics and associated with individual cognitions. Our method achieves an area under the receiver operating characteristic curve of 0.807 ± 0.046 in the internal validation data set and of 0.707 (P = 0.007) in the external testing data set, which shows improvements compared to conventional methods. The method further suggests that, at the local level, the abnormal dynamical functional network states are characterized by decreased connectivity strength and increased connectivity variability at different spatial scales. At the network level, the abnormal states are featured by scale-specifically altered modularity and all-scale decreased efficiency. Low tendencies to stay in abnormal states and high state transition variabilities are significantly associated with high general, language and executive functions. Overall, our work supports the deficits in multiscale brain dynamical functional networks detected by the deep learning method as reliable and meaningful neural alternation underpinning subjective cognitive decline.
Cardiovascular Disease Risk Factor Control in People With and Without HIV
Authors: Silverberg Michael J , Levine Tory M , Lea Alexandra N , Williams Andrew E , Alexeeff Stacey E , Bryant Kendall , Cavassini Matthias , Flamm Jason A , Hare C Bradley , Ingle Suzanne M , Justice Amy C , Lam Jennifer O , Sterling Stacy A , Horberg Michael A , Satre Derek D
Published: January 2024

Background

Management of hypertension, dyslipidemia, diabetes and other modifiable factors may mitigate the cardiovascular disease (CVD) risk in people with human immunodeficiency virus (HIV, PWH) compared with people without HIV (PWoH).

Methods

This was a retrospective cohort study of 8285 PWH and 170 517 PWoH from an integrated health system. Risk factor control was measured using a novel disease management index (DMI) accounting for amount/duration above treatment goals (0% to 100% [perfect control]), including 2 DMIs for hypertension (diastolic and systolic blood pressure), 3 for dyslipidemia (low-density lipoprotein, total cholesterol, triglycerides), and 1 for diabetes (HbA1c). CVD risk by HIV status was evaluated overall and in subgroups defined by DMIs, smoking, alcohol use, and overweight/obesity in adjusted Cox proportional hazards models.

Results

PWH and PWoH had similar DMIs (80%–100%) except for triglycerides (worse for PWH) and HbA1c (better for PWH). In adjusted models, PWH had an elevated risk of CVD compared with PWoH (hazard ratio [HR], 1.18; 95% confidence interval [CI], 1.07–1.31). This association was attenuated in subgroups with controlled dyslipidemia and diabetes but remained elevated for PWH with controlled hypertension or higher total cholesterol. The strongest HIV status association with CVD was seen in the subgroup with frequent unhealthy alcohol use (HR, 2.13; 95% CI, 1.04–4.34).

Conclusions

Control of dyslipidemia and diabetes, but not hypertension, attenuated the HIV status association with CVD. The strong association of HIV and CVD with frequent unhealthy alcohol use suggests enhanced screening and treatment of alcohol problems in PWH is warranted.
Integrated Genomic and Social Network Analyses of SARS-CoV-2 Transmission in the Healthcare Setting
Authors: Keehner Jocelyn , Abeles Shira R , Longhurst Christopher A , Horton Lucy E , Myers Frank E , Riggs-Rodriguez Lindsay , Ahmad Mohammed , Baxter Sally , Boussina Aaron , Cantrell Kalen , Cardenas Priscilla , De Hoff Peter , El-Kareh Robert , Holland Jennifer , Ikeda Daryn , Kurashige Kirk , Laurent Louise C ,   for the SEARCH Alliance, Aigner Stefan , Andersen Kristian G , Anderson Catelyn , Baer Nathan A , Barber Tom , Bauk Marco , Beck Jennifer N , Belda-Ferre Pedro , Betty Maryann , Birmingham Amanda , Castro-Martinez Anelizze , Cheung Willi , De Hoff Peter , Fisch Kathleen M , Gangavarapu Karthik , Gargano Isabella , Hakim Abbas , Harsono Shania , Henson Benjamin , Hobbs Charlotte , Holmes Jacqueline , Jepsen Kristen , Knight Rob , Kurzban Ezra , Laurent Louise C , Marotz Clarisse A , Matteson Nathaniel L , Moshiri Niema , Ngo Toan T , Ostrander Tyler R , Perkins Sarah , Plascencia Ashley , Rivera Andrea , Rivera Ariana , Salido Rodolfo A , Sathe Shashank , Seaver Phoebe , Schwab Madison , Veder Anthony , Yeo Gene W , Zeller Mark , Lucas Andrew , Pride David , Sathe Shashank , Tran Allen R , Vasylyeva Tetyana I , Yeo Gene , Knight Rob , Wertheim Joel O , Torriani Francesca J
Published: January 2024

Background

Infection prevention (IP) measures are designed to mitigate the transmission of pathogens in healthcare. Using large-scale viral genomic and social network analyses, we determined if IP measures used during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic were adequate in protecting healthcare workers (HCWs) and patients from acquiring SARS-CoV-2.

Methods

We performed retrospective cross-sectional analyses of viral genomics from all available SARS-CoV-2 viral samples collected at UC San Diego Health and social network analysis using the electronic medical record to derive temporospatial overlap of infections among related viromes and supplemented with contact tracing data. The outcome measure was any instance of healthcare transmission, defined as cases with closely related viral genomes and epidemiological connection within the healthcare setting during the infection window. Between November 2020 through January 2022, 12 933 viral genomes were obtained from 35 666 patients and HCWs.

Results

Among 5112 SARS-CoV-2 viral samples sequenced from the second and third waves of SARS-CoV-2 (pre-Omicron), 291 pairs were derived from persons with a plausible healthcare overlap. Of these, 34 pairs (12%) were phylogenetically linked: 19 attributable to household and 14 to healthcare transmission. During the Omicron wave, 2106 contact pairs among 7821 sequences resulted in 120 (6%) related pairs among 32 clusters, of which 10 were consistent with healthcare transmission. Transmission was more likely to occur in shared spaces in the older hospital compared with the newer hospital (2.54 vs 0.63 transmission events per 1000 admissions, P < .001).

Conclusions

IP strategies were effective at identifying and preventing healthcare SARS-CoV-2 transmission.
Forensic features and phylogenetic structure survey of four populations from southwest China via the autosomal insertion/deletion markers
Authors: Zhang Han , Yang Meiqing , Zhang Hongling , Ren Zheng , Wang Qiyan , Liu Yubo , Jin Xiaoye , Ji Jingyan , Feng Yuhang , Cai Changsheng , Ran Qianchong , Li Chengtao , Huang Jiang
Published: January 2024

Insertion/Deletion (InDel) polymorphisms, characterized by their smaller amplicons, reduced mutation rates, and compatibility with the prevalent capillary electrophoresis (CE) platforms in forensic laboratories, significantly contribute to the advancement and application of genetic analysis. Guizhou province in China serves as an important region for investigating the genetic structure, ethnic group origins, and human evolution. However, DNA data and the sampling of present-day populations are lacking, especially about the InDel markers. Here, we reported data on 47 autosomal InDels from 592 individuals from four populations in Guizhou (Han, Dong, Yi, and Chuanqing). Genotyping was performed with the AGCU InDel 50 kit to evaluate their utility for forensic purposes and to explore the population genetic structure. Our findings showed no significant deviations from Hardy-Weinberg and linkage equilibriums. The combined power of discrimination (CPD) and the combined power of exclusion (CPE) for each population demonstrated that the kit could be applied to forensic individual identification and was an effective supplement for parentage testing. Genetic structure analyses, including principal component analysis, multidimensional scaling, genetic distance calculation, STRUCTURE, and phylogenetic analysis, highlighted that the genetic proximity of the studied populations correlates with linguistic, geographical, and cultural factors. The observed genetic variances within four research populations were less pronounced than those discerned between populations across different regions. Notably, the Guizhou Han, Dong, and Chuanqing populations showed closer genetic affiliations with linguistically similar groups than the Guizhou Yi. These results underscore the potential of InDel markers in forensic science and provide insights into the genetic landscape and human evolution in multi-ethnic regions like Guizhou.

Key points
Deciphering Factors Linked With Reduced Severe Acute Respiratory Syndrome Coronavirus 2 Susceptibility in the Swiss HIV Cohort Study
Authors: Abela Irene A , Hauser Anthony , Schwarzmüller Magdalena , Pasin Chloé , Kusejko Katharina , Epp Selina , Cavassini Matthias , Battegay Manuel , Rauch Andri , Calmy Alexandra , Notter Julia , Bernasconi Enos , Fux Christoph A , Leuzinger Karoline , Perreau Matthieu , Ramette Alban , Gottschalk Jochen , Schindler Eméry , Wepf Alexander , Marconato Maddalena , Manz Markus G , Frey Beat M , Braun Dominique L , Huber Michael , Günthard Huldrych F , Trkola Alexandra , Kouyos Roger D ,   Swiss HIV Cohort Study, Abela I A , Aebi-Popp K , Anagnostopoulos A , Battegay M , Bernasconi E , Braun D L , Bucher H C , Calmy A , Cavassini M , Ciuffi A , Dollenmaier G , Egger M , Elzi L , Fehr J , Fellay J , Furrer H , Fux C A , Günthard H F , Hachfeld A , Haerry D , Hasse B , Hirsch H H , Hoffmann M , Hösli I , Huber M , Jackson-Perry D , Kahlert C R , Kaiser L , Keiser O , Klimkait T , Kouyos R D , Kovari H , Kusejko K , Labhardt N , Leuzinger K , Martinez de Tejada B , Marzolini C , Metzner K J , Müller N , Nemeth J , Nicca D , Notter J , Paioni P , Pantaleo G , Perreau M , Rauch A , Salazar-Vizcaya L , Schmid P , Speck R , Stöckle M , Tarr P , Trkola A , Wandeler G , Weisser M , Yerly S
Published: January 2024

Background

Factors influencing susceptibility to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remain to be resolved. Using data from the Swiss HIV Cohort Study on 6270 people with human immunodeficiency virus (HIV) and serologic assessment for SARS-CoV-2 and circulating human coronavirus (HCoV) antibodies, we investigated the association of HIV-related and general parameters with SARS-CoV-2 infection.

Methods

We analyzed SARS-CoV-2 polymerase chain reaction test results, COVID-19–related hospitalizations, and deaths reported to the Swiss HIV Cohort Study between 1 January 2020 and 31 December 2021. Antibodies to SARS-CoV-2 and HCoVs were determined in prepandemic (2019) and pandemic (2020) biobanked plasma samples and compared with findings in HIV-negative individuals. We applied logistic regression, conditional logistic regression, and bayesian multivariate regression to identify determinants of SARS-CoV-2 infection and antibody responses to SARS-CoV-2 in people with HIV.

Results

No HIV-1–related factors were associated with SARS-CoV-2 acquisition. High prepandemic HCoV antibodies were associated with a lower risk of subsequent SARS-CoV-2 infection and with higher SARS-CoV-2 antibody responses on infection. We observed a robust protective effect of smoking on SARS-CoV-2 infection risk (adjusted odds ratio, 0.46 [95% confidence interval, .38–.56]; P < .001), which occurred even in previous smokers and was highest for heavy smokers.

Conclusions

Our findings of 2 independent protective factors, smoking and HCoV antibodies, both affecting the respiratory environment, underscore the importance of the local immune milieu in regulating susceptibility to SARS-CoV-2.
Recent advances in the epithelial barrier theory
Authors: Pat Yagiz , Yazici Duygu , D’Avino Paolo , Li Manru , Ardicli Sena , Ardicli Ozge , Mitamura Yasutaka , Akdis Mübeccel , Dhir Raja , Nadeau Kari , Agache Ioana , Ogulur Ismail , Akdis Cezmi A
Published: January 2024

The epithelial barrier theory links the recent rise in chronic non-communicable diseases, notably autoimmune and allergic disorders, to environmental agents disrupting the epithelial barrier. Global pollution and environmental toxic agent exposure have worsened over six decades because of uncontrolled growth, modernization, and industrialization, affecting human health. Introducing new chemicals without any reasonable control of their health effects through these years has led to documented adverse effects, especially on the skin and mucosal epithelial barriers. These substances, such as particulate matter, detergents, surfactants, food emulsifiers, micro- and nano-plastics, diesel exhaust, cigarette smoke, and ozone, have been shown to compromise the epithelial barrier integrity. This disruption is linked to the opening of the tight-junction barriers, inflammation, cell death, oxidative stress, and metabolic regulation. Consideration must be given to the interplay of toxic substances, underlying inflammatory diseases, and medications, especially in affected tissues. This review article discusses the detrimental effect of environmental barrier-damaging compounds on human health and involves cellular and molecular mechanisms.
Autoclaving time-related reduction in amino acid digestibility of poultry meal in broiler chickens and growing pigs
Authors: Sung Jung Yeol , Park Chan Sol , Ragland Darryl , Caroline González-Vega J , Wiltafsky-Martin Markus K , Adeola Olayiwola
Published: January 2024

Poultry meal, a rendered byproduct of poultry slaughter, is a valuable protein source in swine and poultry diets because of its highly digestible protein content and balanced amino acid (AA) profile. Rendering of poultry meal may reduce its AA digestibility because of heat damage to the byproduct. The effect of heat damage on AA digestibility of poultry meal may be different between broiler chickens and growing pigs. For this reason, the objective of this study was to determine the effect of autoclaving time on standardized ileal digestibility (SID) of AA in poultry meal fed to broiler chickens and growing pigs. Poultry meal from the same batch was autoclaved at 134 °C for 0, 30, 60, 90, 120, 150, or 180 min to produce seven heat-treated samples. Eight experimental diets were formulated. Poultry meal served as the sole source of nitrogen in seven diets that each contained one of the heat-treated byproducts and a nitrogen-free diet was formulated to assess basal ileal endogenous losses of AA. In experiment 1, 656 male broiler chickens (initial body weight = 719 ± 97 g) at day 18 post hatching were assigned to the eight diets in a randomized complete block design with body weight as a blocking factor. On day 23, birds were euthanized by CO2 asphyxiation and dissected for the collection of ileal digesta. In experiment 2, 16 barrows (initial body weight = 23.3 ± 0.7 kg) were surgically fitted with T-cannulas at the distal ileum and allotted to a duplicate 8 × 4 incomplete Latin square design with the eight diets and four periods. Each experimental period consisted of 5-day adaptation and 2-day ileal digesta collection periods. Data for experiments 1 and 2 were pooled and analyzed as a 2 × 7 factorial treatment arrangement with the effects of species (i.e., pigs and broiler chickens) and autoclaving time (i.e., 0 to 180 min) as the two factors. Increasing autoclaving time decreased SID of nitrogen and all AA in both species, but the decrease in SID values except for leucine was greater (interaction, P < 0.05) or tended to be greater in pigs compared with broiler chickens. Given the species differences in AA utilization response to the severity of heat damage, target species should be considered when using SID of AA values of poultry meal in diet formulation.
Direct visualization of ribosomes in the cell-free system revealed the functional evolution of aminoglycoside
Authors: Tomono Junta , Asano Kosuke , Chiashi Takuma , Suzuki Masato , Igarashi Masayuki , Takahashi Yoshiaki , Tanaka Yoshikazu , Yokoyama Takeshi
Published: January 2024

The rapid emergence of multi-drug-resistant bacteria has raised a serious public health concern. Therefore, new antibiotic developments have been highly desired. Here, we propose a new method to visualize antibiotic actions on translating ribosomes in the cell-free system under macromolecular crowding conditions by cryo-electron microscopy, designated as the DARC method: the Direct visualization of Antibiotic binding on Ribosomes in the Cell-free translation system. This new method allows for acquiring a more comprehensive understanding of the mode of action of antibiotics on the translation inhibition without ribosome purification. Furthermore, with the direct link to biochemical analysis at the same condition as cryo-EM observation, we revealed the evolution of 2-DOS aminoglycosides from dibekacin (DBK) to arbekacin (ABK) by acquiring the synthetic tailored anchoring motif to lead to stronger binding affinity to ribosomes. Our cryo-EM structures of DBK and ABK bound ribosomes in the cell-free environment clearly depicted a synthetic tailored γ-amino-α-hydroxybutyryl (HABA) motif formed additional interactions with the ribosome enhancing antibiotic bindings. This new approach would be valuable for understanding the function of antibiotics for more efficient drug development.
Locating algorithm of steel stock area with asynchronous advantage actor-critic reinforcement learning
Authors: Cho Young-in , Kim Byeongseop , Yoon Hee-Chang , Woo Jong Hun
Published: January 2024

In the steel stockyard of the shipyard, the sorting work to relocate the steel plates already stacked to retrieve the target steel plate on the fabrication schedule is labor-consuming work requiring the operation of overhead cranes. To reduce the sorting work, there is a need for a method of stacking the steel plates in order of fabrication schedules when the steel plates arrive at the shipyard from the steel-making companies. However, the conventional optimization algorithm and heuristics have limitations in determining the optimal stacking location of steel plates because the real-world stacking problems in shipyards have vast solution space in addition to the uncertainty in the arrival order of steel plates. In this study, reinforcement learning is applied to the development of a real-time stacking algorithm for steel plates considering the fabrication schedule. Markov decision process suitable for the stacking problem is defined, and the optimal stacking policy is learned using an asynchronous advantage actor-critic algorithm. The learned policy is tested on several problems by varying the number of steel plates. The test results indicate that the proposed method is effective for minimizing the use of cranes compared with other metaheuristics and heuristics for stacking problems.
The orphan G protein–coupled receptor 141 expressed in myeloid cells functions as an inflammation suppressor
Authors: Sawabe Atsuya , Okazaki Shogo , Nakamura Akira , Goitsuka Ryo , Kaifu Tomonori
Published: January 2024

G protein–coupled receptors (GPCRs) regulate many cellular processes in response to various stimuli, including light, hormones, neurotransmitters, and odorants, some of which play critical roles in innate and adaptive immune responses. However, the physiological functions of many GPCRs and the involvement of them in autoimmune diseases of the central nervous system remain unclear. Here, we demonstrate that GPR141, an orphan GPCR belonging to the class A receptor family, suppresses immune responses. High GPR141 messenger RNA levels were expressed in myeloid-lineage cells, including neutrophils (CD11b + Gr1+), monocytes (CD11b + Gr1−Ly6C+ and CD11b + Gr1−Ly6C−), macrophages (F4/80+), and dendritic cells (CD11c+). Gpr141  −/− mice, which we independently generated, displayed almost no abnormalities in myeloid cell differentiation and compartmentalization in the spleen and bone marrow under steady-state conditions. However, Gpr141 deficiency exacerbated disease conditions of experimental autoimmune encephalomyelitis, an autoimmune disease model for multiple sclerosis, with increased inflammation in the spinal cord. Gpr141  −/− mice showed increased CD11b + Gr1+ neutrophils, CD11b + Gr1− monocytes, CD11c+ dendritic cells, and CD4+ T cell infiltration into the experimental autoimmune encephalomyelitis–induced spinal cord compared with littermate control mice. Lymphocytes enriched from Gpr141  −/− mice immunized with myelin oligodendrocyte glycoprotein 35–55 produced high amounts of interferon-γ, interleukin-17A, and interleukin-6 compared with those from wild-type mice. Moreover, CD11c+ dendritic cells (DCs) purified from Gpr141  −/− mice increased cytokine production of myelin oligodendrocyte glycoprotein 35–55–specific T cells. These findings suggest that GPR141 functions as a negative regulator of immune responses by controlling the functions of monocytes and dendritic cells and that targeting GPR141 may be a possible therapeutic intervention for modulating chronic inflammatory diseases.
Enabling children to learn from religions whilst respecting their rights: against monopolies of influence
Authors: Gheaus Anca
Published: January 2024

John Tillson argues, on grounds of children’s well-being, that it is impermissible to teach them religious views. I defend a practice of pluralistically advocating religious views to children. As long as there are no monopolies of influence over children, and as long as advocates do not use coercion, deceit, or manipulation, children can greatly benefit without having their rational abilities subverted, or incurring undue risk to form false beliefs. This solution should counter, to some extent, both perfectionist and antiperfectionist reasons against initiating children into religions.
The diagnosis and management of solid pseudopapillary epithelial neoplasm of the pancreas in a resource-limited setting: two cases from Cameroon
Authors: Shu Chinonso P , Ngock George F F , Lisongwe Masango M G , Ndayong Nkwayeb R , Djomaleu Arnaud R , Yecke Macky F E , Brown James A
Published: January 2024

Solid pseudopapillary epithelial neoplasm (SPEN) of the pancreas is a rare tumor of low malignant potential that occurs most often in young females. Imaging and histopathology are necessary to confirm the diagnosis as most have no symptoms. Lack of access to these technologies in sub-Saharan Africa contributes to the difficulty in making an early and accurate diagnosis, and hence, impedes treatment. We present two cases of SPEN of the pancreas in young female patients at a rural, teaching hospital in Cameroon. The diagnosis was made only with histopathology. Computed tomography scan with intravenous contrast was essential to planning a safe surgical resection. Both patients had complete surgical resection with good results.
Du Bois on Government and Democratic Debate
Authors: Jeffers Chike
Published: January 2024

I argue that the second chapter of W.E.B. Du Bois’s The Souls of Black Folk has been underappreciated as a work of political philosophy, as Du Bois offers us in it a way of understanding what a government is and how to evaluate when a government is good. I relate Du Bois’s account of governmental leadership in that chapter to his critique of Booker T. Washington as a nongovernmental leader in chapter 3 of Souls. While doing this, I also pay attention to Du Bois’s account of democratic debate in chapter 3.
Combining genotype with height-adjusted kidney length predicts rapid progression of ADPKD
Authors: Chen Eugene W C , Chong Jiehan , Valluru Manoj K , Durkie Miranda , Simms Roslyn J , Harris Peter C , Ong Albert C M
Published: January 2024

Introduction

Our main objective was to identify baseline prognostic factors predictive of rapid disease progression in a large unselected clinical autosomal dominant polycystic kidney disease (ADPKD) cohort.

Methods

A cross-sectional analysis was performed in 618 consecutive ADPKD patients assessed and followed-up for over a decade. A total of 123 patients (19.9%) had reached kidney failure by the study date. Data were available for the following: baseline eGFR (n = 501), genotype (n = 549), baseline ultrasound mean kidney length (MKL, n = 424) and height-adjusted baseline MKL (HtMKL, n = 377). Rapid disease progression was defined as an annualized eGFR decline (∆eGFR) of >2.5 mL/min/year by linear regression over 5 years (n = 158). Patients were further divided into slow, rapid and very rapid ∆eGFR classes for analysis. Genotyped patients were classified into several categories: PKD1 (T, truncating; or NT, non-truncating), PKD2, other genes (non-PKD1 or -PKD2), no mutation detected or variants of uncertain significance.

Results

A PKD1-T genotype had the strongest influence on the probability of reduced baseline kidney function by age. A multivariate logistic regression model identified PKD1-T genotype and HtMKL (>9.5 cm/m) as independent predictors for rapid disease progression. The combination of both factors increased the positive predictive value for rapid disease progression over age 40 years and of reaching kidney failure by age 60 years to 100%. Exploratory analysis in a subgroup with available total kidney volumes showed higher positive predictive value (100% vs 80%) and negative predictive value (42% vs 33%) in predicting rapid disease progression compared with the Mayo Imaging Classification (1C–E).

Conclusion

Real-world longitudinal data confirm the importance of genotype and kidney length as independent variables determining ∆eGFR. Individuals with the highest risk of rapid disease progression can be positively selected for treatment based on this combination.
Seroprevalence of dengue and chikungunya viruses among urban refugees in Klang Valley, Malaysia
Authors: Sahimin Norhidayu , Low Zhao Xuan , Hassandarvish Pouya , Mohd Hanapi Izzah Ruzana , Mohd Zain Siti Nursheena , Yahaya Hasmawati , Abu Bakar Sazaly
Published: January 2024

Background

Mosquito-borne diseases pose a significant global public health threat, with Malaysia's Klang Valley experiencing numerous outbreaks in densely populated urban areas.

Methods

This study aimed to estimate the seroprevalence of anti-dengue and anti-chikungunya antibodies among urban refugees in the Klang Valley, Malaysia, and identify associated risk factors.

Results

High seroprevalence of anti-dengue immunoglobulin G (IgG) and IgM (60.0% [confidence interval {CI} 55.39 to 64.48] and 9.2% [CI 6.77 to 12.25], respectively) were observed among refugees >18 years of age (χ22=11.720, p=0.003), Kachin ethnicity (χ28=72.253, p<0.001), without formal education (χ21=3.856, p=0.050), homes near waste disposal sites (χ21=10.378, p=0.001) and refugees who have experienced flooding (χ21=5.460, p=0.019). Meanwhile, the overall seroprevalence of anti-chikungunya IgG and IgM was 9.7% (CI 7.15 to 12.73) and 10.8% (CI 8.09 to 13.93), respectively, with ages 12–18 years (χ22=6.075, p=0.048), Rohingya ethnicity (χ28=31.631, p<0.001) and homes close to waste disposal sites (χ21=3.912, p=0.048) being significant risk factors. Results showed a link to poor environmental living conditions, with an increase in the vector population with higher availability of breeding sites and thus exposure to dengue and chikungunya virus.

Conclusions

Health education among the community is the key to disease prevention, as there are no specific antiviral drugs for treatment and limited vaccine availability.
SPHK1/S1P/S1PR pathway promotes the progression of peritoneal fibrosis by mesothelial‐mesenchymal transition
Authors: Zhao Tingting , Ding Tao , Sun Zhengyu , Shao Xin , Li Shuangxi , Lu Hongtao , Yuan Ji‐hang , Guo Zhiyong
Published: January 2024

Long‐term exposure to non‐physiologically compatible dialysate inevitably leads to peritoneal fibrosis (PF) in patients undergoing peritoneal dialysis (PD), and there is no effective prevention or treatment for PF. Sphingosine‐1‐phosphate (S1P) is a bioactive sphingolipid produced after catalysis by sphingosine kinase (SPHK) 1/2 and activates signals through the S1P receptor (S1PR) via autocrine or paracrine. However, the role of SPHK1/S1P/S1PR signaling has never been elucidated in PF. In our research, we investigated S1P levels in peritoneal effluents and demonstrated the role of SPHK1/S1P/S1PR pathway in peritoneal fibrosis. It was found that S1P levels in peritoneal effluents were positively correlated with D/P Cr (r = 0.724, p < .001) and negatively correlated with 4 h ultrafiltration volume (r = −0.457, p < .001). S1PR1 and S1PR3 on peritoneal cells were increased after high glucose exposure in vivo and in vitro. Fingolimod was applied to suppress S1P/S1PR pathway. Fingolimod restored mouse peritoneal function by reducing interstitial hyperplasia, maintaining ultrafiltration volume, reducing peritoneal transport solute rate, and mitigating the protein expression changes of fibronectin, vimentin, α‐SMA, and E‐cadherin induced by PD and S1P. Fingolimod preserved the morphology of the human peritoneal mesothelial cells, MeT‐5A, and moderated the mesothelial‐mesenchymal transition (MMT) process. We further delineated that SPHK1 was elevated in peritoneal cells after high glucose exposure and suppression of SPHK1 in MeT‐5A cells reduced S1P release. Overexpression of SPHK1 in MeT‐5A cells increased S1P levels in the supernatant and fostered the MMT process. PF‐543 treatment, targeting SPHK1, alleviated deterioration of mouse peritoneal function. In conclusion, S1P levels in peritoneal effluent were correlated with the deterioration of peritoneal function. SPHK1/S1P/S1PR pathway played an important role in PF.
Hemolymph exosomes inhibit Spiroplasma eriocheiris infection by promoting Tetraspanin‐mediated hemocyte phagocytosis in crab
Authors: Ma Yubo , Yao Yu , Meng Xiang , Fu Hui , Li Jiaying , Luan Xiaoqi , Liu Min , Liu Hongli , Gu Wei , Hou Libo , Meng Qingguo
Published: January 2024

Exosomes released from infected cells are thought to play an important role in the dissemination of pathogens, as well as in host‐derived immune molecules during infection. As an intracellular pathogen, Spiroplasma eriocheiris is harmful to multiple crustaceans. However, the immune mechanism of exosomes during Spiroplasma infection has not been investigated. Here, we found exosomes derived from S. eriocheiris‐infected crabs could facilitate phagocytosis and apoptosis of hemocytes, resulting in increased crab survival and suppression of Spiroplasma intracellular replication. Proteomic analysis revealed the altered abundance of EsTetraspanin may confer resistance to S. eriocheiris, possibly by mediating hemocyte phagocytosis in Eriocheir sinensis. Specifically, knockdown of EsTetraspanin in E. sinensis increased susceptibility to S. eriocheiris infection and displayed compromised phagocytic ability, whereas overexpression of EsTetraspanin in Drosophila S2 cells inhibited S. eriocheiris infection. Further, it was confirmed that intramuscular injection of recombinant LEL domain of EsTetraspanin reduced the mortality of S. eriocheiris‐infected crabs. Blockade with anti‐EsTetraspanin serum could exacerbate S. eriocheiris invasion of hemocytes and impair hemocyte phagocytic activity. Taken together, our findings prove for the first time that exosomes modulate phagocytosis to resist pathogenic infection in invertebrates, which is proposed to be mediated by exosomal Tetraspanin, supporting the development of preventative strategies against Spiroplasma infection.
Cancer-Related Fatigue Is Associated With Objective Measures of Physical Function Before and After a Clinical Exercise Program: A Retrospective Analysis
Authors: Marker Ryan J. , Wechsler Stephen , Leach Heather J.
Published: January 2024

Background:

Cancer-related fatigue (CRF) is a common symptom reported by survivors of cancer. CRF is associated with reduced self-reported physical function, but associations with objective measures of physical function are less robust. Exercise programs have been shown to improve both CRF and objective physical function, but the interaction of exercise, CRF, and function has not been explored.

Methods:

Retrospective data were collected from baseline (n = 420) and final assessments (n = 234) of survivors who participated in a 3-month clinical exercise program. Assessments included measures of CRF (Functional Assessment of Chronic Illness Therapy–Fatigue) and physical function (6-minute walk test, usual and fast gait speed, 30-second sit-to-stand test, and the Timed Up and Go test). Multiple regression analyses investigated associations between CRF and physical function before and after the program. CRF and functional changes following the program were calculated and associations investigated with multiple regressions.

Results:

All measures of CRF and physical function significantly improved following the program (P < .01). CRF was associated with all functional measures at baseline (standardized β = −0.18 to 0.29, P < .01) and final assessments (r = −0.27 to 0.26, P < .01). Changes in CRF were associated with changes in function (standardized β = −0.12 to 0.23, P < .05), except usual gait speed (P = .17).

Conclusion:

This investigation demonstrated associations between CRF and objective physical function before and after participation in an exercise program. The 3-way interaction between CRF, physical function, and exercise can be used clinically to personalize rehabilitation strategies. Future studies should investigate changes in CRF and function during an exercise program.
Evidence of “Repeated Admission Bias” Among Those Who Use Injection Drugs Across 2 Decades of US Treatment Admissions: 2000–2020
Authors: Bormann Nicholas L. , Arndt Stephan
Published: January 2024

Objectives

Encounter-based datasets like the Treatment Episode Dataset—Admissions (TEDS-A) are used for substance use–related research. Although TEDS-A reports the number of previous treatment admissions, a limitation is this reflects encounters, not people. We sought to quantify the methodologic bias incorporated by using all encounters versus initial encounters and assess if this risk is evenly distributed across all routes of drug administration.

Methods

TEDS-A 2000–2020 dataset with nonmissing primary substance data was used. Of the data, 3.17% were missing the usual administration route, and 11.9% were missing prior admission data. Prior admissions are documented as 0 through 4, then binned for 5 or greater (5+). Risk of admission bias was defined as odds ratio (ORRAB): odds of total admissions relative to the odds of the first admission. Bootstrap confidence intervals were generated (5000 iterations) across administration routes and demographics; however, their widths were <0.0055 and not reported.

Results

There were 38,238,586 admissions over the 21 years, with 13,865,517 (41.2%) first admissions. Of all admissions, 15.7% indicated injection drug use (IDU); 26.3% of encounters reporting IDU were in the 5+ group. This resulted in an ORRAB of 1.77. White enrollees had an elevated ORRAB (1.05), whereas among Latinos, ORRAB was low (0.74).

Conclusions

Using encounter-based datasets can introduce bias when including all admissions versus exclusively initial treatment episodes. This report is the first to quantify this bias and shows that individuals with IDU are at highest risk for returning to treatment, thereby over-representing this method of use when all encounters are used.
An Inpatient Protocol for the Treatment of Methamphetamine Withdrawal in Patients With and Without Opioid Use Disorder
Authors: Wilens Timothy E. , Wilson Ronan L. H. , Beltrame Lia , Taylor Adam , O’Connell James
Published: January 2024

Objective

Increasing rates of methamphetamine (METH) use, use disorders, and related overdoses are a growing public health problem. There are a lack of protocols addressing METH intoxication and withdrawal symptoms that manifest during acute withdrawal treatment resulting in inpatient management difficulties and premature discharges. This report presents a novel treatment protocol comprised of behavior-targeted and pharmacological components that aims to reduce the intensity and duration of METH intoxication and withdrawal related symptoms during early treatment, improve retention, and provide clinicians with a tool to meet this growing problem.

Methods

The protocol was developed by a team of addiction physicians and other clinical staff. Clinical and administrative staff at a community acute stabilization unit were trained and the protocol was implemented with patients presenting with METH use. Pharmacological interventions, including ascorbic acid, antipsychotics, and other sedatives are discussed, as are behavior-based orders. A retrospective quality assurance examination was conducted on patient characteristics and outcomes as well as focus groups with nursing staff.

Results

A total of 23 patients consecutively admitted to the unit used the protocol (100% male). Most patients (67%) displayed symptoms of METH use or withdrawal. Behavior-related interventions were used in 52% of patients, while 48% received behavior-related and pharmacological measures. Patient completion of the protocol was 83%, and the protocol’s utility was supported by nursing staff.

Conclusions

This retrospective evaluation of a novel METH withdrawal treatment protocol suggests feasibility, tolerability, and preliminary evidence of effectiveness, providing clinicians with a new tool that requires further study.
An Emphasis on the Role of Peroneus Brevis to Peroneus Longus Transfer in Progressive Collapsing Flatfoot Deformity
Authors: Maher Moustafa Alaa , Khedr Ahmed , Kholeif Ahmed , Radwan Y. A. , Reda Mansour Ali M. , Haleem Amgad M.
Published: January 2024

The role of the peroneal tendons in progressive collapsing flatfoot deformity (PCFD), also traditionally known as posterior tibial tendon dysfunction, is likely overlooked and almost certainly understudied. We explored the impact of peroneus brevis (PB) to peroneus longus (PL) transfer in the adult population with flexible PCFD deformities class A1 (flexible hindfoot valgus), B1 (flexible midfoot abduction), and C1 (flexible forefoot varus) as an augmentative measure combined with various bony procedures with proper assessment functionally, clinically, and radiologically. PB to PL tendon transfer poses a simple procedure dealing with muscle imbalance between the medial and lateral columns of the foot. It deals with the new understanding of the PCFD complex as a three-dimensional deformity. It works mainly on the axial plane to limit midfoot abduction and strongly augments the PL acting on the sagittal plane to address the forefoot varus. Finally, to a lesser extent, it deals with the coronal plane of hindfoot valgus, eliminating the primary evertor of the foot (PB) while simultaneously strengthening the PL, which contributes to the medial longitudinal and transverse arches of the foot, therefore decreasing the possibility of lateral column overload commonly caused by the Evans osteotomy through reducing pressure across the calcaneocuboid joint. This procedure is preferably indicated for flexible PCFD deformities class (A1, B1, and C1), yet is contraindicated in neuromuscular deformities with peroneal nerve palsy.

Level of Evidence: Level IV.
The effect of emotion regulation on the emotional modulation of pain and nociceptive flexion reflex
Authors: Toledo Tyler A. , Vore Claudia N. , Huber Felicitas A. , Rhudy Jamie L.
Published: January 2024

Positive emotions inhibit pain, whereas negative emotions facilitate pain. Thus, many psychosocial interventions capitalize on this emotion–pain relationship to improve patients' abilities to regulate emotion (ie, reduce negative emotion, increase positive emotion), influence nociception, and manage pain. This study extended the existing literature to examine whether emotion regulation procedures could influence emotional modulation of the nociceptive flexion reflex (NFR), a marker of spinal nociception. To elicit emotion, 2 blocks of pleasant, neutral, and unpleasant pictures were presented. In block 1, participants were asked to passively view pictures during which painful electric stimulations were delivered to evoke pain and the NFR. Valence, arousal, corrugator electromyogram, and skin conductance response were used to measure emotional responses to pictures. To manipulate emotion regulation, participants were randomized to either suppress (downregulate) or enhance (upregulate) their emotion during block 2 (other procedures same as block 1). Instructions to suppress decreased subjective and physiological responding to emotional pictures, reduced emotional modulation of pain, and generally decreased NFR magnitude (regardless of picture content). Instructions to enhance emotion increased subjective responding to emotional pictures but did not alter physiological responding to pictures or emotional modulation of pain/NFR in predictable ways. Results imply that downregulation/suppression of negative emotions may work best to reduce pain facilitation. Furthermore, this study contributes to the existing literature that shows that pain and pain signaling is tightly coupled with emotional states and that emotion regulation can impact pain perception.
Liraglutide in Obese or Overweight Individuals With Stable Bipolar Disorder
Authors: McElroy Susan L. , Guerdjikova Anna I. , Blom Thomas J. , Mori Nicole , Romo-Nava Francisco
Published: January 2024

Background

Obesity is common among persons with bipolar disorder (BD). Liraglutide 3.0 mg/d subcutaneous injection is indicated for chronic weight management and associated with minimal adverse neuropsychiatric effects. This study evaluated whether liraglutide 3 mg/d reduced body weight, improved metabolic factors and eating psychopathology, and was safe and well tolerated in persons with stable BD who were obese (body mass index [BMI] >30 kg/m2) or overweight (BMI ≥27 kg/m2) with at least one weight-related comorbidity.

Methods

This was a 40-week, randomized (1:1 ratio), placebo-controlled, double-blind, parallel-group, 2-arm clinical trial of liraglutide targeted to 3.0 mg/d (in combination with a reduced-calorie diet and increased physical activity) in 60 participants with stable BD who were obese or overweight. Primary outcome was percent change in body weight from baseline to study end. Secondary outcomes included percentage of patients who lost ≥5% of baseline body weight, and changes in metabolic variables and measures of eating psychopathology.

Results

There were no significant baseline differences between the 29 liraglutide recipients and the 31 placebo recipients, except that liraglutide recipients had higher levels of binge eating and lower levels of high-density lipoprotein cholesterol. Compared with placebo, liraglutide was associated with significantly greater reductions in percent change in body weight, percentage of participants who lost at least 5% of body weight, and reductions in weight, BMI, hemoglobin A1c levels, binge eating, and hunger. Liraglutide was well tolerated.

Conclusions

Liraglutide 3 mg/d may be efficacious and safe for weight loss in individuals with stable BD and obesity or overweight.

Registration details

ClinicalTrials.gov (NCT03158805).