bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 19 Cleveland Cord Blood Center (CCBC) Best Practices Throughout the COVID-19 Pandemic and How It Impacted Collection of Cord Blood Units
Authors: Bobik-Kurz Kathy , Laster Candice , Chase JoAnn , Boucher Susan , Wood Bridget , Laughlin Mary , Finney Marcie
Published: September 2022

Introduction

Our commitment to provide quality cord blood units (CBUs) to patients in need was challenged with the outbreak of COVID-19 and the pandemics continued impact through early 2022. We continually monitored the ever-evolving COVID-19 public health threat to make adjustments to our practices to achieve optimal collections while maintaining the safety and quality of our CBUs.

Objective

The CCBC continued collections at all five collection sites with a brief mandated pause at our California site due to hospital restrictions. We maintained minimal staffing at the cord blood center to reduce the number of employees impacted should an exposure occur. Donors were screened upon admission for symptoms, exposure, positive testing, and recent vaccination, and donors with identified risks were excluded from collection.

Methods

Our study design takes a retrospective look at data collected from the onset of the COVID-19 pandemic through December 2021 compared to data from 2018-2019. Factors included were birth numbers, number of patients testing positive for COVID-19, and staffing shortages due to coordinator illness with COVID-19.

Results

We saw limited impact to our collection staff at the hospital or on site at the CCBC. Our biggest reduction of donors consented was between 2019 and 2020, which we attribute to the COVID peak and introduction of vaccinations. Most sites were trending downward for consenting on a yearly basis before COVID-19 at a rate of 6%-10% per year; during 2019-2020 we saw 19%, but the trend has returned to 8% from 2020-2021. This same trending occurred during the ZIKA outbreak. There was no further data review to determine if these mothers would have been excluded for other reasons. We collected a total of 15,561 units between 2018 and 2019 and a total of 10,121 units between 2020 and 2021.

Discussion

Overall productivity of the collections was not dramatically affected by our response to the COVID-19 pandemic. Further research at time of pre-consent, to determine if the mother would have been ineligible to donate for reasons other than COVID-19, would have given us a more accurate count of donors lost for reasons related to the COVID-19 pandemic.
Abstract 22 CellStor Transfer Freezing Bag: Reliable Closed System for Complex Cord Blood Sample Processing and CD34+ Hematopoietic Stem Cell Cryopreservation
Authors: Kasthuri Srikumar , Abhaya Mayur , Padhiar Chirayu , Rajan Balaji , Anbalagan Jayanthi , Rengarajan Srinivas
Published: September 2022

Introduction

Hematopoietic stem cell (HSC) transplants are effective in the treatment of numerous disorders. Proper processing and storage of umbilical cord blood (UCB) and peripheral blood (PB) HSCs is invaluable for therapeutic applications. Although automated sample processing methods exist, they are unable to accommodate low volume, viscous, fibrin clotted, partially hemolyzed, or otherwise complex samples, resulting in the loss of precious HSCs. The CellBios single-use transfer freezing bag was designed to process peripheral and cord blood samples and freeze HSCs, including from those with the above-mentioned problems. Here we demonstrate the utility of these transfer freezing bags to salvage problematic UCB samples and recover precious HSC material suitable for banking and therapeutics.

Objective

The objective of this study was to develop a closed UCB sample processing and cryopreservation solution that is amenable to easy manual operation, can deliver excellent HSC viability and recovery, can eliminate contaminating red blood cells (RBCs), and is capable of processing complex/defective starting samples that are incompatible with conventional automated processing systems into therapeutic grade HSC banks.

Methods

We studied 100 randomly selected UCB samples, from various centers throughout India, that were processed and prepared for cryopreservation using our transfer freezing bag. We recorded the pre- and post-sample processing volumes, total nucleated cell counts (TNCC), hematocrit (HCT), CD34+ cell viability, and recovery.

Results

Study results showed the following: 94% vs 98% CD34+ cell viability post processing, 77% vs 85% total mononuclear cell viability, 69% vs 85% TNCC recovery in problematic vs normal samples, respectively. It was possible to achieve low RBC carryover –91% HCT reduction post-processing in normal samples; more importantly, problematic samples also had RBC removal evidenced by HCT reduction of 45%.

Discussion

We have demonstrated efficient removal of RBCs to alleviate post-transplantation issues and maximized CD34+ HSC recovery in both normal and problematic UCB samples. Crucially, it was possible to salvage precious CB HSCs from defective samples that would be lost had they been processed in conventional automated workflows. The CellBios CellStor Transfer Freezing Bag Set offers best in class performance in preparing umbilical cord blood samples for cryostorage.
Abstract 23 A First Insight into the Validity of Post-Thaw Cell Recovery, Viability, and Potency Over Time
Authors: Liu Lin , McDonald Trish , Elwood Ngaire
Published: September 2022

Introduction

Testing of a thawed segment or representative sample of a cord blood unit (CBU) for cell recovery, viability, and potency forms part of pre-release testing. Not all CBUs that have had pre-release testing completed are shipped for transplant, due to postponed or cancelled shipment request, and are therefore kept in the inventory until they are searched again. In an effort to identify these CBUs for future expedited release, the World Marrow Donor Association (WMDA) initiated a project to flag them as “Ready to Ship” in the WMDA Search & Match Service. However, it is not known how long post-thaw results are valid before they must be repeated on another thaw. Such information can be beneficial not only for transplant centers to better assess CBU suitability but also for Cord Blood Banks (CBBs) to avoid unnecessarily exhausting their precious samples.

Objective

This study aimed to provide a first insight into the validity of post-thaw results over various lengths of time.

Methods

Nineteen CBUs, collected between 2003 and 2015 at the BMDI CBB and that had post-thaw testing performed twice, were analyzed for change in the total nucleated cell (TNC) recovery, total CD34 cell recovery, CD34 cell viability, and CFU-GM counts between two thaws.

Results

The 19 CBUs were grouped into 4 groups based on their storage time between thaws. An average decrease in TNC recovery of 5.3% from first thaw to second thaw was observed for the entire dataset (P = .015). Four CBUs with a greater than 10% decrease had a bag TNC greater than 25 × 108. Individual CBU data is shown in Figure 1. No significant change between thaws was seen with total CD34 recovery (P = .738) or CD34 viability (n = 9 pairs, P = .354). A large variation in CFU-GM counts was observed between thaws. It is worth noting that all CBUs met CBB release criteria of >60% TNC recovery and that CD34 viabilities were above 70% (FACT requirement) in both thaws.

Discussion

While results need to be confirmed on a larger dataset, our preliminary data shows very little change in post-thaw cell recovery and viability over various lengths of time (2 months-12 years), suggesting post-thaw results may be valid for longer than 10 years.
Abstract 24 Improving Cord Blood Unit Selection and Optimizing Manufacturing of a Unique Cord Blood-Derived Product (DUOC-01)
Authors: Ozamiz April , Shoulars Kevin , Noldner Pamela , Shaz Beth , Kurtzberg Joanne
Published: September 2022

Introduction

DUOC-01 are microglia-like cells derived from umbilical cord blood CD14-positive monocytes, which have been shown to induce remyelination in murine models of demyelination. Intrathecal DUOC-01 administration is being tested clinically in two phase I studies. First, DUOC-01 is being tested as a bridging therapy for pediatric patients with inherited leukodystrophies undergoing unrelated donor cord blood transplantation. Second, DUOC-01 is being tested in a phase Ia dose escalation study in patients with primary progressive multiple sclerosis.

Objective

DUOC-01 is manufactured from an HLA-matched cryopreserved cord blood unit (CBU). The CBU is thawed and cultured for 21 days under specific conditions, and the resulting DUOC-01 is harvested and formulated with hydrocortisone for intrathecal administration. Cell dosing per patient is limited by DUOC-01 yield, which is highly variable; therefore, there is great need to increase DUOC-01 yield and optimize manufacturing for more consistency.

Methods

(1) For the identification of optimal CBU selection, units are screened using small scale DUOC-01 cultures derived from CBU bag segments, which are then scored (0-4). In order to assess the value, we performed screening followed by DUOC-01 manufacturing and correlated the screening score to the DUOC-01 yield. (2) We assessed multiple variables to optimize DUOC-01 manufacturing including media volume and temperature, fetal bovine serum (FBS) lot variability, and culture container material.

Results

(1) 5/13 segments scored high (defined as ≥2) while the remaining 8/13 scored low (<2). All 5 high-scored CBUs resulted in high yield (defined as ≥1.64 total cells/cm2). Of the 8 low-scored segments, 4 were low yield and 4 were high yield. (2) Comparison of different FBS lots did not show a significant change in DUOC-01 yield. Furthermore, media volume and temperature did not influence product yield. The choice of container material substantially impacted culture yields and cell viability (Figure 1).

Discussion

In order to increase cell yield and improve product consistency, we confirmed the value of the CBU segment screening assay and discovered the potential importance of culture container material. More experiments are needed to optimize and finalize product manufacturing.
Comparative analysis of genome-encoded viral sequences reveals the evolutionary history of flavivirids (family Flaviviridae)
Authors: Bamford Connor G G , de Souza William M , Parry Rhys , Gifford Robert J
Published: September 2022

Flavivirids (family Flaviviridae) are a group of positive-strand ribonucleic acid (RNA) viruses that pose serious risks to human and animal health on a global scale. Here, we use flavivirid-derived deoxyribonucleic acid (DNA) sequences, identified in animal genomes, to reconstruct the long-term evolutionary history of family Flaviviridae. We demonstrate that flavivirids are >100 million years old and show that this timing can be combined with dates inferred from co-phyletic analysis to produce a cohesive overview of their evolution, distribution, and diversity wherein the main flavivirid subgroups originate in early animals and broadly co-diverge with major animal phyla. In addition, we reveal evidence that the ‘classical flaviviruses’ of vertebrates, most of which are transmitted via blood-feeding arthropod vectors, originally evolved in haematophagous arachnids and later acquired the capacity to be transmitted by insects. Our findings imply that the biological properties of flavivirids have been acquired gradually over the course of animal evolution. Thus, broad-scale comparative analysis will likely reveal fundamental insights into their biology. We therefore published our results via an open, extensible, database (Flavivirid-GLUE), which we constructed to facilitate the wider utilisation of genomic data and evolution-related domain knowledge in flavivirid research.
Hsa_circ_0000877 facilitates the progression of diffuse large B-cell lymphoma by miR-370-3p/mitogen-activated protein kinase kinase kinase kinase 4/Hippo pathway
Authors: Zhan Chengzhi , Zhou Hanyi , Zhang Wanyong , Si Cheng
Published: September 2022

Diffuse large B-cell lymphoma (DLBCL) originates from B lymphocytes and is a fatal hematological malignancy. Circular RNAs have been increasingly reported as a promising biological target for cancer therapy, but their role in DLBCL remains poorly studied. Relative expression levels of has_circ_0000877 (circ_0000877), microRNA-370-3p (miR-370-3p), and mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4) were assessed by quantitative real-time PCR. Western blot analysis was employed to measure protein levels. Cell Counting Kit-8 assay and 5-ethynyl-2′-deoxyuridine (EdU) assay were used to detect the proliferation of TMD8 and U2932 cells. Cell cycle and apoptosis were investigated by flow cytometry. Transwell assay was used to analyze cell migration and invasion. Molecular interaction was determined by dual-luciferase reporter assay and RNA immunoprecipitation assay. The protein expression of Ki67 in tumor tissues of mice was detected by immunohistochemistry assay. The expression of circ_0000877 was markedly elevated in DLBCL tissues and cell lines. The decreased expression of circ_0000877 significantly inhibited proliferation, migration, and invasion of DLBCL cell lines. In addition, silencing circ_0000877 promoted cell apoptosis and induced cell cycle arrest in G0/G1 phase. Then, miR-370-3p directly interacted with circ_0000877 and MAP4K4. Circ_0000877 promoted MAP4K4 level by sponging miR-370-3p. MAP4K4 depletion inhibited the activation of Hippo pathway. Finally, circ_0000877 silencing significantly prevented the growth of DLBCL cells in vivo. Our findings revealed that circ_0000877 could regulate the malignant evolution of DLBCL by miR-370-3p/MAP4K4/Hippo pathway.
Overexpression of lncRNA TCLlnc1 in gastric cancer predicts postoperative distant recurrence and poor survival
Authors: Hu Kan , Zhang Yugui , Rong Jun , Deng Wensheng , Xiao Benping
Published: September 2022

TCLlnc1 was characterized as a lncRNA with oncogenic roles in T cell lymphoma, whereas its role in other diseases is unknown. We then explored the involvement of TCLlnc1 in gastric cancer. Paired gastric cancer and nontumor tissues from 66 gastric cancer patients were used to extract total RNA samples, which were used to perform RT-qPCRs to determine the expression of TCLlnc1. Plasma samples from these 66 gastric cancer patients and 66 healthy controls were also used to detect circulating TCLlnc1. Correlations of TCLlnc1 in both plasma and tissue samples with patients’ clinical data were analyzed by chi-square t-test. The diagnostic value of TCLlnc1 for early-stage gastric cancer was analyzed with the receiver operating characteristic curve. A 5-year follow-up study was performed to explore the prognostic value of TCLlnc1 for the survival of gastric cancer patients. TCLlnc1 expression in tissue was increased in gastric cancer. Plasma TCLlnc1 was also increased in gastric cancer. Plasma TCLlnc1 was closely correlated with TCLlnc1 in gastric cancer tissues, but not TCLlnc1 in nontumor tissues. TCLlnc1 in plasma was only correlated with tumor distant metastasis, but not other clinical data. TCLlnc1 in plasma showed promising diagnostic value for stage I and II gastric cancer. Increased accumulation of TCLlnc1 was closely correlated with distant recurrence and poor survival during a 5-year follow-up. Therefore, TCLlnc1 is overexpressed in gastric cancer predicts postoperative distant recurrence and poor survival.
Revisiting miRNA-21 as a Therapeutic Strategy for Myocardial Infarction: A Systematic Review
Authors: Sothivelr Vivisana , Hasan Mohammad Y. , Mohd Saffian Shamin , Zainalabidin Satirah , Ugusman Azizah , Mahadi Mohd K.
Published: September 2022

Several types of cardiovascular cells use microRNA-21 (miR-21), which has been linked to cardioprotection. In this study, we systematically reviewed the results of published papers on the therapeutic effect of miR-21 for myocardial infarction. Studies described the cardioprotective effects of miR-21 to reduce infarct size by improving angiogenesis, antiapoptotic, and anti-inflammatory mechanisms. Results suggest that cardioprotective effects of miR-21 may work synergistically to prevent the deterioration of cardiac function during postischemia. However, there are other results that indicate that miR-21 positively regulates tissue fibrosis, potentially worsening a postischemic injury. The dual functionalities of miR-21 occur through the targeting of genes and signaling pathways, such as PTEN, PDCD4, KBTBD7, NOS3, STRN, and Spry-1. This review provides insights into the future advancement of safe miR-21–based genetic therapy in the treatment of myocardial infarction.
Implementation of an In Vitro Experimental Setup Simulating Pulmonary Dissolution Following the Inhalation of Radioactive Particulate Material
Authors: Saviotti Agnese , Porta Alessandro Antonio , Campi Fabrizio , Derudi Marco
Published: September 2022

Given the need for criteria to control the radiation doses due to radionuclide inhalation, in 1994 the International Commission on Radiological Protection presented a classification for radioactive compounds based on their pulmonary absorption rates. The Commission classified the compounds into fast, moderate, and slow categories and assigned to each material a default absorption class. Nevertheless, the proposed categories do not always resemble the actual behavior of the classified materials in the pulmonary environment. Therefore, the Commission itself suggested the assessment of the inhalation risk of a particulate substance referring to an in vivo study using the same material. Since it is not possible to trace in literature in vivo studies analyzing the physiological behavior of the totality of inhalable radioactive materials, the Commission suggested adopting in vitro systems simulating the pulmonary mechanism. For this reason, in the last 50 y, many simulating setups have been implemented, but none of these seemed to reproduce the lung dissolution dynamics effectively as the results were not comparable with the ones obtained using in vivo techniques. This paper aims to describe an innovative experimental apparatus implemented as an attempt to add another step toward the realization of a gold standard. In particular, the system was validated with BaSO4 particulate, and the resulting error with respect to the physiological expected value figured as less than 4%. The system was then employed for the lung dissolution tests of radioactive graphite extracted from Politecnico di Milano’s nuclear reactor to assess the radiobiological risk due to a slow lung absorption process that workers might run into during the reactor decommissioning.
A double hyperautofluorescent ring in a 33-year-old-female patient
Authors: da Palma Mariana M. , Marrra Molly , Pennesi Mark E.
Published: September 2022

Purpose:

To describe the clinical phenotype and molecular diagnosis of a patient with atypical presentation of Enhanced S-cone Syndrome.

Methods:

This is a case report of a patient that underwent best-corrected visual acuity, slit-lamp exam, fundus exam, autofluorescence, optical coherence tomography, kinetic perimetry, full-field electroretinography. Genetic testing was performed via next-generation sequencing.

Results:

A 33-years-old female patient presented with mild nyctalopia but normal rod function measured by electroretinogram and foveoschisis on OCT. She also presented a double hyperautofluorescent ring on autofluorescence. Genetic testing found a pathogenic variant c.925C>G (p.Arg309Gly) and a likely pathogenic variant c.299C>T (p.Arg77Trp) in NR2E3 gene.

Discussion:

Enhanced S-cone Syndrome may present without the pathognomonic findings of decreased rod function on ERG, suggesting the importance of genetic testing in retinal diseases for diagnosis.
Leber hereditary optic neuropathy: new and emerging therapies
Authors: Davila-Siliezar Pamela , Carter Michael , Milea Dan , Lee Andrew G.
Published: September 2022

Purpose of review

To review recent therapeutic advances in Leber hereditary optic neuropathy (LHON).

Recent findings

Idebenone, a synthetic analog of ubiquinone (Coenzyme Q10) is an antioxidant and component of the mitochondrial electron transport chain. Since the initial approval of the drug in 2015 in Europe, recent trials have evaluated its role as prolonged treatment in LHON. Gene therapy has recently emerged as a promising alternative for the treatment of LHON. Among several investigations, RESCUE and REVERSE are two phase 3 clinical trials of gene therapy in patients with LHON in early stages. Results in these trials have shown a bilateral visual acuity improvement with unilateral intravitreal injections at 96 weeks and sustained visual improvement after 3 years of treatment. The most recent REFLECT phase 3 clinical trial in LHON has shown significant improvement of vision after bilateral intravitreal injections compared with the group that received unilateral injections.

Historically, LHON has been considered an untreatable disease, but recent developments show that new pharmacological and gene therapy approaches may lead to visual recovery. Further studies are needed to support these data.
A Mother-Child Dyadic Approach to Evaluating Subclinical Cardiovascular Disease in Young Children
Authors: Muchira James M. , Mogos Mulubrhan F. , Park Chorong , Logan Jeongok , Piano Mariann R.
Published: September 2022

Background

Cardiovascular (CV) risk factors can be transmitted from mothers to their children. However, it is challenging to measure and identify subclinical CV risk in young children using traditional CV risk methods and metrics.

Objective

The purpose of this study was to determine the feasibility of recruiting mother-child dyads and measuring arterial stiffness (pulse wave velocity, augmentation index/pressure), blood pressure (BP), BP circadian pattern, specifically nocturnal BP dipping, and CV health metrics in mothers and in children aged 1 to 5 years.

Methods

All BP and arterial stiffness measures were obtained using the noninvasive automated oscillometric Mobil-O-Graph device. Also measured were blood cholesterol level; glucose level; body mass index (BMI); and smoking, diet, and physical activity history. Descriptive statistics were used for assessing recruitment feasibility and Pearson correlations for mother-child associations.

Results

Thirty-five mother-child dyads completed the protocol. Recruitment reach was 89% and retention rate was 80%. Mothers were 34.3 ± 5.4 years old with a mean systolic BP (SBP) of 114.6 ± 9.5 mm Hg and BMI of 26.0 ± 6.5. Children were 3 ± 1.4 years old with a mean SBP of 103.3 ± 9.4 mm Hg and BMI z-scores of −0.3 ± 1.5. Arterial stiffness parameters were within normal ranges for mothers and children. Twenty-three percent of mothers did not exhibit nocturnal dipping (<10% decrease between day and nighttime SBP). Maternal SBP was positively correlated with child BMI z-scores (r = 0.42, P = .022) as well as mother-child augmentation pressure (r = 0.51, P = .010).

Conclusions

Our findings support using a mother-child approach and novel noninvasive approaches to assess and target CV risk in mothers and their young children.
Quality Improvement to Promote Sepsis Reassessment
Authors: DeGregoris Jana P. , Bandong Lyza , White Tameka , Brennan Mary M.
Published: September 2022

Background:

Implementation of the Surviving Sepsis Campaign (SSC) guidelines into practice has demonstrated improved outcomes.

Local Problem:

Compliance with a sepsis protocol, based on the SSC guidelines, in an urban teaching hospital was below the national average.

Methods:

A pre- and posttest intervention design was used to improve clinician knowledge, confidence, and compliance with the protocol.

Interventions:

Educational modules were developed on the SSC guidelines and reminder system alerts (RSA) for timely revaluation of patients with sepsis and lactate monitoring were implemented.

Results:

A total of 33 (48%) clinicians participated. There was an increase in knowledge, documentation of sepsis reassessment, and serum lactate monitoring. There was an improvement in clinician perceptions following the initiative.

Conclusions:

The results demonstrate that education, combined with RSAs, can improve protocol knowledge and compliance.
Reducing Carbapenem-Resistant Enterobacteriaceae Using the Targeted Solution Tool
Authors: Ragonese Barbara , Mularoni Alessandra , Valeri Andrea , Campanella Maria , Corso Brigida , Fazzina Maria Luisa , Barone Maria Angela , Arena Giuseppe , Lombardo Rosario , Luca Angelo
Published: September 2022

Background:

Carbapenem-resistant Enterobacteriaceae (CRE) is a worldwide urgent health problem. Hand hygiene (HH) is an effective intervention to reduce the spread of CRE.

Local Problem:

In 2017, an increase in the rate of health care–associated (HA) CRE colonization was observed in a large multiorgan transplant center in Italy. This study aimed to reduce the HA-CRE colonization rates by improving HH compliance.

Methods:

A pre-/post-intervention project was conducted from November 2017 through December 2020.

Interventions:

The DMAIC (Define, Measure, Analyze, Improve, and Control) framework was used to implement the HH Targeted Solution Tool (TST).

Results:

Hand hygiene compliance increased from 49% to 76.9% after the Improve phase (P = .0001), and to 81.9% after the second Control phase (P = .0001). The rate of HA-CRE decreased from 24.9% to 5.6% (P = .0001).

Conclusions:

Using the DMAIC framework to implement the TST can result in significant improvements in HH compliance and HA-CRE colonization rates.
Characteristics, Treatment, and Prognosis of Elemental Mercury Intoxication in Children
Authors: Güven Deniz , Özbek İmran
Published: September 2022

Objectives

Mercury exposure is common and can be toxic, especially in children. Children are often drawn to elemental mercury because of its density, color, and proclivity to form beads.

Methods

We present data on 49 children with mercury intoxication (MI) and 60 children with mercury exposure from Turkey.

Results

The most common source of mercury was broken thermometer in schools. Inhaling mercury vapor was the most common route of exposure. The median exposure time was 6 (6–16) hours in the MI group, and the time to 1st symptoms was 10 (0–24) hours. In the MI group, the median blood mercury level was 21 μg/L (13–32.3), the median spot urine mercury level was 40 μg/L (7.66–78), and the median 24-hour urine mercury level was 25.8 μg/L (11–64). The most common symptoms in patients with MI were malaise, muscle pain, muscle cramps, abdominal pain, nausea, headache, and decreased appetite. The patients were treated with n-acetyl cysteine, 2,3-dimercaptopropane sulfonic acid, D-penicillamine, and meso 2,3-dimercaptosuccinic acid. A positive correlation was found between exposure time and urinary mercury level in the MI group (r = 0.793, P < 0.001). A positive moderate correlation was found between exposure time and blood level in the mercury exposure group (r = 0.535, P < 0.00). The neurological and systemic examinations of patients were all normal at the 1st follow-up visit 1 month after discharge.

Conclusions

Diagnosis, removal of the exposure source, and use of chelation therapy can result in complete resolution of the signs and symptoms of MI.
Disentangled multi-subject and social behavioral representations through a constrained subspace variational autoencoder (CS-VAE)
Authors: Yi Daiyao , Musall Simon , Churchland Anne , Padilla-Coreano Nancy , Saxena Shreya
Published: September 2022

Effectively modeling and quantifying behavior is essential for our understanding of the brain. Modeling behavior in naturalistic settings in social and multi-subject tasks remains a significant challenge. Modeling the behavior of different subjects performing the same task requires partitioning the behavioral data into features that are common across subjects, and others that are distinct to each subject. Modeling social interactions between multiple individuals in a freely-moving setting requires disentangling effects due to the individual as compared to social investigations. To achieve flexible disentanglement of behavior into interpretable latent variables with individual and across-subject or social components, we build on a semi-supervised approach to partition the behavioral subspace, and propose a novel regularization based on the Cauchy-Schwarz divergence to the model. Our model, known as the constrained subspace variational autoencoder (CS-VAE), successfully models distinct features of the behavioral videos across subjects, as well as continuously varying differences in social behavior. Our approach vastly facilitates the analysis of the resulting latent variables in downstream tasks such as uncovering disentangled behavioral motifs, the efficient decoding of a novel subject’s behavior, and provides an understanding of how similarly different animals perform innate behaviors.
Prefrontal representation of affective stimuli: importance of stress, sex, and context
Authors: Wallace Tyler , Myers Brent
Published: September 2022

Major depressive disorder diminishes health-related quality-of-life and disproportionality impacts females. Negative life events predict the onset of depressive symptoms including negative mood, anhedonia, and social withdrawal. While the neurobiology of affective illness is not completely understood, structural and functional changes in the ventromedial prefrontal cortex (vmPFC) associate with mood and anxiety disorders. Rodent studies have investigated the prefrontal impact of chronic stress, a preclinical model of mood disruption. However, ex vivo slice and postmortem histological studies have focused largely on males and yielded mixed results. Although genetically-defined recordings in behaving animals of both sexes have not been reported. Here, we hypothesized that chronic variable stress (CVS) would reduce the neural processing of affective stimuli in the infralimbic region of rodent vmPFC region. To test this hypothesis, we targeted expression of a fluorescent calcium indicator, GCaMP6s, to infralimbic pyramidal cells. In males, CVS reduced infralimbic responses to social interaction and restraint stress but increased responses to novel objects and food reward. In contrast, females did not have CVS-induced changes in infralimbic activity, which was partially dependent on ovarian status. Collectively, these results indicate that both male and female vmPFC pyramidal cells encode social, stress, and reward stimuli. However, chronic stress effects are sex-dependent and behavior-specific. Ultimately, these findings extend the understanding of chronic stress-induced prefrontal dysfunction and indicate that sex is a critical factor for cortical processing of affective stimuli.

Significance

Mood disorders are often preceded by stressful experiences and exhibit sex differences in prevalence. Further, affective illness is frequently accompanied by changes in prefrontal cortical function. However, the neurobiology that underlies sex-specific cortical processing of affective stimuli is poorly understood. Therefore, the current studies employ cell type-specific calcium photometry to determine the effects of chronic stress on ventromedial prefrontal cortex (vmPFC) activity in male and female rats. Our results indicate that chronic stress exposure differentially alters vmPFC encoding of social, stress, and reward stimuli. Moreover, the sex-specific effects of chronic stress are partially mediated by ovarian hormones. Ultimately, our results indicate that prolonged stress alters vmPFC function in a context-dependent and sex-specific manner, contributing to the biological bases for sex differences in emotional processing.
Cardiovascular Hemodynamics in Mice with Tumor Necrosis Factor Receptor - Associated Factor 2 Mediated Cytoprotection in the Heart
Authors: Marshall Andrea G. , Neikirk Kit , Vue Zer , Beasley Heather K. , Garza-Lopez Edgar , Vang Larry , Barongan Taylor , Evans Zoe , Crabtree Amber , Spencer Elsie , Anudokem Josephs , Parker Remy , Davis Jamaine , Stephens Dominique , Damo Steven , Pham Thuy T. , Gomez Jose A. , Exil Vernat , Dai Dao-fu , Murray Sandra , Entman Mark L. , Taffet George E , Hinton Antentor O. , Reddy Anilkumar K.
Published: September 2022

Many studies in mice have demonstrated that cardiac-specific innate immune signaling pathways can be reprogrammed to modulate inflammation in response to myocardial injury and improve outcomes. While the echocardiography standard parameters of left ventricular (LV) ejection fraction, fractional shortening, and end-diastolic diameter, and others, are used to assess cardiac function, their dependency on loading conditions somewhat limit their utility in completely reflecting the contractile function and global cardiovascular efficiency of the heart. A true measure of global cardiovascular efficiency should include of the interaction between the ventricle and the aorta (ventriculo-vascular coupling, VVC) as well as measures of aortic impedance and pulse wave velocity. We measured cardiac Doppler velocities, blood pressures, along with VVC, aortic impedance, and pulse wave velocity to evaluate global cardiac function in mouse model of cardiac-restricted low levels TRAF2 overexpression that conferred cytoprotection in the heart. While previous studies reported that response to myocardial infraction and reperfusion was improved in the TRAF2 overexpressed mice, we found that TRAF2 mice had significantly lower cardiac systolic velocities and accelerations, diastolic atrial velocity, lower aortic pressures and rate-pressure product, lower LV contractility and relaxation, and lower stroke work when compared to littermate control mice. Also, we found significantly longer aortic ejection time, isovolumic contraction and relaxation times, and significantly higher mitral early/atrial ratio, myocardial performance index, and ventricular vascular coupling in the TRAF2 overexpression mice compared to their littermate controls. We found no significant differences in the aortic impedance and pulse wave velocity. While the reported tolerance to ischemic insults in TRAF2 overexpression mice may suggest enhanced cardiac reserve, our results indicate a diminished cardiac function in these mice.
Role of procalcitonin in chronic kidney diseases patients undergoing renal therapy
Authors: Khan Abdul Ghaffar , Akhtar Nosheen , Tariq Zartasha , Arif Muhammad
Published: September 2022

medRxiv has withdrawn this preprint owing to plagiarism. Therefore, this work should not be cited as a reference for this project.
Mechanical regulation of Titin N2B-us conformation and its binding to FHL2
Authors: Sun Yuze , Huang Wenmao , Le Shimin , Yan Jie
Published: September 2022

The 572 amino acids unique sequence on titin N2B element (N2B-us) is known to regulate the passive elasticity of muscle as an elastic spring. It also serves as a hub for cardiac hypertrophic signaling by interacting with multiple proteins such as FHL1(Sheikh et al, 2008), FHL2(Lange et al, 2002), and Erk2(Perkin et al, 2015). N2B-us is thought to be an intrinsically disordered region. In addition, N2B-us bears force; therefore, the functions of N2B-us are likely regulated by mechanical stretching. In the work, we investigated the conformation of N2B-us as well as its force-dependent interaction with FHL2 using a combination of AlphaFold2 predictions and single-molecule experimental validation. Surprisingly, a stable alpha/beta structural domain (~115 a.a.) was predicted and confirmed in N2B-us, which can be mechanically unfolded at forces greater than 5 pN. More than twenty FHL2 LIM domain binding sites were predicted to spread throughout N2B-us including the regions cryptic in the structural domain. Mechanosensitive binding of FHL2 to N2B-us is revealed in single-molecule manipulation experiments. Together, the results unveil several previously unknown aspects of the N2B-us conformations and its force-dependent interactions with FHL2, which provides new insights into the physiological functions of the force-bearing N2B-us region.
Neural cognitive signals during spontaneous movements in the macaque
Authors: Tremblay Sébastien , Testard Camille , DiTullio Ron W. , Inchauspé Jeanne , Petrides Michael
Published: September 2022

The single neuron basis of cognitive processing in primates has mostly been studied in laboratory settings where movements are severely restricted. It is unclear, therefore, how natural movements might affect neural signatures of cognition in the brain. Moreover, studies in mice indicate that body movements, when measured, account for most of the neural dynamics in the cortex. To examine this issue, we recorded from single neuron ensembles in the prefrontal cortex in moving monkeys performing a cognitive task and characterized eyes, head, and body movements using video tracking. Despite significant trial-to-trial movement variability, single neuron tuning could be precisely measured and decision signals accurately decoded on a single-trial basis. Creating or abolishing spontaneous movements through head restraint and task manipulations had no measurable impact on neural responses. However, encoding models showed that uninstructed movements explained as much neural variance as task variables, with most of them aligned to task events. These results demonstrate that cognitive signals in the cortex are robust to natural movements, but also that unmeasured movements are potential confounds in cognitive neurophysiology experiments.
Crystal structure, PIXEL calculations of intermolecular interaction energies and solid-state characterization of the herbicide isoxaflutole
Authors: Schinke Jascha , Gelbrich Thomas , Griesser Ulrich J.
Published: September 2022

In the isoxaflutole molecule {systematic name: (5-cyclopropyl-1,2-oxazol-4-yl)[2-(methylsulfonyl)-4-(trifluoromethyl)phenyl]methanone; C15H12F3NO4S}, the 1,2-oxazole and methanone fragments form an almost coplanar unit, whereas the methanone and phenyl mean planes are inclined by an angle of more than 60°. This conformation differs fundamentally from all other known examples of the 1,2-oxazol-4-yl(phenyl)methanone fragment and is ascribed to the presence of the bulky methylsulfonyl para substituent at the phenyl ring. PIXEL calculations reveal that the largest contributions to the stabilization of the crystal persist within a columnar arrangement of molecules along the twofold screw axis and in interactions between adjacent columns related by an inversion operation. Both these intra-column and inter-column motifs are dominated by the dispersion energy term but also display additional significant stabilization effects as a result of three short intermolecular C—H...O contacts involving the methanesulfonyl-O atoms.
Food price dynamics and regional clusters: machine learning analysis of egg prices in China
Authors: Liu Chang , Zhou Lin , Höschle Lisa , Yu Xiaohua
Published: September 2022

Purpose

The study uses machine learning techniques to cluster regional retail egg prices after 2000 in China. Furthermore, it combines machine learning results with econometric models to study determinants of cluster affiliation. Eggs are an inexpensiv, nutritious and sustainable animal food. Contextually, China is the largest country in the world in terms of both egg production and consumption. Regional clustering can help governments to imporve the precision of price policies and help producers make better investment decisions. The results are purely driven by data.

Design/methodology/approach

The study introduces dynamic time warping (DTW) algorithm which takes into account time series properties to analyze provincial egg prices in China. The results are compared with several other algorithms, such as TADPole. DTW is superior, though it is computationally expensive. After the clustering, a multinomial logit model is run to study the determinants of cluster affiliation.

Findings

The study identified three clusters. The first cluster including 12 provinces and the second cluster including 2 provinces are the main egg production provinces and their neighboring provinces in China. The third cluster is mainly egg importing regions. Clusters 1 and 2 have higher price volatility. The authors confirm that due to transaction costs, the importing areas may have less price volatility.

Practical implications

The machine learning techniques could help governments make more precise policies and help producers make better investment decisions.

Originality/value

This is the first paper to use machine learning techniques to cluster food prices. It also combines machine learning and econometric models to better study price dynamics.
Impact on recommendation performance of online review helpfulness and consistency
Authors: Park Jaeseung , Li Xinzhe , Li Qinglong , Kim Jaekyeong
Published: September 2022

Purpose

The existing collaborative filtering algorithm may select an insufficiently representative customer as the neighbor of a target customer, which means that the performance in providing recommendations is not sufficiently accurate. This study aims to investigate the impact on recommendation performance of selecting influential and representative customers.

Design/methodology/approach

Some studies have shown that review helpfulness and consistency significantly affect purchase decision-making. Thus, this study focuses on customers who have written helpful and consistent reviews to select influential and representative neighbors. To achieve the purpose of this study, the authors apply a text-mining approach to analyze review helpfulness and consistency. In addition, they evaluate the performance of the proposed methodology using several real-world Amazon review data sets for experimental utility and reliability.

Findings

This study is the first to propose a methodology to investigate the effect of review consistency and helpfulness on recommendation performance. The experimental results confirmed that the recommendation performance was excellent when a neighbor was selected who wrote consistent or helpful reviews more than when neighbors were selected for all customers.

Originality/value

This study investigates the effect of review consistency and helpfulness on recommendation performance. Online review can enhance recommendation performance because it reflects the purchasing behavior of customers who consider reviews when purchasing items. The experimental results indicate that review helpfulness and consistency can enhance the performance of personalized recommendation services, increase customer satisfaction and increase confidence in a company.
Exploring the value of mentorship for women police officers
Authors: Lavender Logan , Todak Natalie
Published: September 2022

Purpose

The paper explores the prevalence of mentorship opportunities for women police officers, the nature of mentorship relationships, and their perceived effect on women’s career advancement.

Design/methodology/approach

Data consist of online surveys (N = 924) with women police officers working in the United States. A content analysis of emergent themes from one open ended survey question was conducted.

Findings

Findings underscore the central importance of mentorship in policing, the lack of mentorship among women due to in-group competition, and participants’ active participation in mentoring future generations of women officers.

Originality/value

Factors contributing to the lack of gender diversity and specifically the retention of women in policing, are not well understood. The underrepresentation of women in coveted specialty assignments and upper ranking positions is also of concern. A possible explanation is that women officers lack role models and networking opportunities that are more readily available to men in this male-dominated field, which could encourage women to remain in law enforcement and assist in their career advancement. As many agencies have or are beginning to establish mentorship programs for women, research focused on the need for and effectiveness of mentorship for women officers is needed.
Exploring the factors influencing consumer preference toward dairy products: an empirical research
Authors: Bahety Pankaj Kumar , Sarkar Souren , De Tanmoy , Kumar Vimal , Mittal Ankesh
Published: September 2022

Purpose

This study aims to identify the major factors influencing the consumers to prefer milk products and also to analyze the awareness level of the Indian consumers.

Design/methodology/approach

In this study, the data is obtained through a structured questionnaire from Indian consumers considering convenience sampling under the nonprobability sampling technique. The consumer preference is explained using a multiple-regression model followed by analysis of variance (ANOVA), which shed insight on the significant differences between the variables that influence consumer preference for dairy products.

Findings

Investigation is done to analyze the factors influencing the consumers' buying behavior toward milk and its products. The results showed that quality, health consciousness, price and availability are the most influencing factors to buy milk products. Quantity of milk showed a significant relationship between age, monthly income and family size.

Research limitations/implications

This study helps marketing managers to frame the marketing strategies based on consumer preference, quality, health consciousness, price and availability. The research outcome will not only be advantageous for the entrepreneurial perspective but also takes care of consumer likeliness. Though the research reveals the opinion of Indian consumers, it limits the likeliness of the western world. Because of the scarcity of resources, several dairy products are unexplored, which could pave the future scope of research.

Originality/value

The novelty of this study is to identify the quality, health consciousness, price and availability are the most influencing factors to buy milk products considering ANOVA and the multiple regression model.
Evolutionary divergence via sexual selection acting on females in a species with sex role reversal
Authors: Hare Robin M. , Kennington W. Jason , Simmons Leigh W.
Published: September 2022

There is much evidence that sexual selection drives the evolutionary divergence of male sexual traits, but little is known of females.

Comparisons between neutral genetic divergence (FST) and phenotypic divergence (PST) among populations can reveal evolutionary responses to selection.

In the bushcricket Kawanaphila nartee, changes in floral food availability cause sex roles to shift from competitive females and choosy males to choosy females and competitive males midway through the breeding season. Males call to attract females, and female auditory spiracle size is under sexual selection. We ask whether selection on females can drive an evolutionary divergence in auditory spiracle size among populations.

We sampled 188 individuals from nine geographic locations and analysed 9478 neutral SNP loci and two phenotypic characters to estimate FST and PST respectively.

We found that PST for female auditory spiracle size far exceeded the global FST, suggesting that female auditory spiracle size is subject to strong directional selection. We relate differences in phenotypic traits to differences in geological and floristic characteristics among the sites.

Our data suggest that variation in sexual selection driven by variation in the floristic community on which this species feeds may contribute to the strength of directional selection acting on female K. nartee among populations.

Together, these findings indicate that divergence among populations can be driven by sexual selection acting on females, even when that selection is temporary and circumscribed.

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