bluuebunny/crossref_metadata_2025 huggingface dataset:
Designing a Shortened Preclinical Basic Science Curriculum: Expert-Derived Recommendations
Authors: Held Natalie , Jimenez Sheilah , Lockspeiser Tai , Adams Jennifer E.
Published: March 2023

Purpose

To generate an expert-derived list of recommendations for how medical schools should approach decisions about the placement of basic science topics within shortened preclinical curricula, which allow for early clinical immersion.

Method

A modified Delphi process was used to develop consensus on recommendations (March–November 2021). The authors performed semistructured interviews with national undergraduate medical education (UME) experts from institutions that previously underwent curricular reforms involving shortened preclinical curricula to elicit perspectives on how decisions were made at their institutions. The authors condensed the findings into a preliminary list of recommendations and distributed this list in 2 survey rounds to a larger group of national UME experts (from institutions that previously underwent curricular reforms or held positions of authority within national UME organizations) to gauge their level of agreement with each recommendation. Recommendations were revised based on participant comments, and those with at least 70% somewhat or strong agreement after the second survey were included in the final comprehensive list of recommendations.

Results

Interviews were conducted with 9 participants and resulted in 31 preliminary recommendations that were then sent via survey to the 40 recruited participants. Seventeen/40 (42.5%) participants completed the first survey, after which 3 recommendations were removed, 5 were added, and 5 were revised based on comments—resulting in 33 recommendations. Twenty-two/38 (57.9%) participants responded to the second survey, after which all 33 recommendations met inclusion criteria. The authors removed 3 recommendations that did not directly address the curriculum reform process and consolidated the final 30 recommendations into 5 succinct, actionable takeaways.

Conclusions

This study generated 30 recommendations (summarized by the authors in 5 succinct takeaways) for medical schools designing a shortened preclinical basic science curriculum. These recommendations reinforce the importance of vertically integrating basic science instruction with explicit clinical relevance into all curricular phases.
Cannabinoid Therapy
Authors: Gewandter Jennifer S. , Edwards Robert R. , Hill Kevin P. , Wasan Ajay D. , Hooker Julia E. , Lape Emma C. , Besharat Soroush , Cowan Penney , Le Foll Bernard , Ditre Joseph W. , Freeman Roy
Published: March 2023

Objective:

Clinical trials of cannabinoids for chronic pain have mixed and often inconclusive results. In contrast, many prospective observational studies show the analgesic effects of cannabinoids. This survey study aimed to examine the experiences/attitudes of individuals with chronic pain who are currently taking, have previously taken, or never taken cannabinoids for chronic pain to inform future research.

Methods:

This study is based on a cross-sectional, web-based survey of individuals with self-reported chronic pain. Participants were invited to participate through an email that was distributed to the listservs of patient advocacy groups and foundations that engage individuals with chronic pain.

Results:

Of the 969 respondents, 444 (46%) respondents reported currently taking, 213 (22%) previously taken, and 312 (32%) never taken cannabinoids for pain. Participants reported using cannabinoids to treat a wide variety of chronic pain conditions. Those currently taking cannabinoids (vs previously) more frequently reported: (1) large improvements from cannabinoids in all pain types, including particularly difficult-to-treat chronic overlapping pain conditions (eg, pelvic pain), (2) improvements in comorbid symptoms (eg, sleep), and (3) lower interference from side effects. Those currently taking cannabinoids reported more frequent and satisfactory communication with clinicians regarding cannabinoid use. Those never taken cannabinoids reported a lack of suggestion/approval of a clinician (40%), illegality (25%), and lack of FDA regulation (19%) as reasons for never trying cannabinoids.

Conclusion:

These findings underscore the importance of conducting high-quality clinical trials that include diverse pain populations and clinically relevant outcomes that if successful, could support FDA approval of cannabinoid products. Clinicians could then prescribe and monitor these treatments similarly to other chronic pain medications.
A Pilot Study to Examine the Effect of Passive Straight Leg Raise Performed During Cardiopulmonary Resuscitation on Cerebral Perfusion Measured by Noninvasive Cerebral Oximetry
Authors: Lorensini Scott , Prakash Shivesh , McNeill David , Spencer Neil , Bihari Shailesh
Published: March 2023

OBJECTIVES:

Passive leg raise (PLR) during cardiopulmonary resuscitation (CPR) is simple and noninvasive maneuver, which can potentially improve patient-related outcomes. Initial CPR guidelines have previously advocated “elevation of the lower extremities to augment artificial circulation during CPR.” There is lack of supporting evidence for this recommendation.

DESIGN:

This was a double cross-over physiologic efficacy randomized study.

SETTING AND PATIENTS:

Study in 10 subjects with in-hospital cardiac arrest for whom CPR was undertaken.

INTERVENTION:

Subjects were randomized to receive two cycles of CPR with PLR followed by two cycles of CPR without PLR (Group I) or vice-versa (Group II). Subjects had their foreheads (right and left) fitted with near infrared spectroscopy (NIRS) electrodes (O3 System-Masimo, Masimo corporation Forty Parker, Irvine CA) while undergoing CPR during the study. NIRS readings, a measure of mixed venous, arterial, and capillary blood oxygen saturation, act as a surrogate measure of cerebral blood perfusion during CPR.

MEASUREMENT AND MAIN RESULTS:

PLR was randomly used “first” in five of them, whereas it was used “second” in the remaining five subjects. In subjects in whom PLR was performed during first two cycles (Group I), NIRS values were initially significantly greater. The performance of PLR during CPR in Group II attenuated the decline in NIRS readings during CPR.

CONCLUSIONS:

PLR during CPR is feasible and leads to augmentation of cerebral blood flow. Furthermore, the expected decline in cerebral blood flow over time during CPR may be attenuated by this maneuver. The clinical significance of these findings will require further investigations.
Spermidine enhances the efficacy of adjuvant in HBV vaccination in mice
Authors: Ito Daisuke , Ito Hiroyasu , Ando Tatsuya , Sakai Yasuhiro , Ideta Takayasu , Ishii Ken J. , Ishikawa Tetsuya , Shimizu Masahito
Published: March 2023

Background: Various vaccine adjuvants have been developed to eliminate HBV from patients with chronic HBV infection. In addition, spermidine (SPD), a type of polyamine, has been reported to enhance the activity of immune cells. In the present study, we investigated whether the combination of SPD and vaccine adjuvant enhances the HBV antigen-specific immune response to HBV vaccination. Methods: Wild-type and HBV-transgenic (HBV-Tg) mice were vaccinated 2 or 3 times. SPD was orally administered in drinking water. Cyclic guanosine monophosphate–AMP (cGAMP) and nanoparticulate CpG-ODN (K3-SPG) were used as the HBV vaccine adjuvants. The HBV antigen-specific immune response was evaluated by measuring the HBsAb titer in blood collected over time and the number of interferon-γ producing cells by enzyme-linked immunospot assay. Results: The administration of HBsAg + cGAMP + SPD or HBsAg + K3-SPG + SPD significantly enhanced HBsAg-specific interferon-γ production by CD8 T cells from wild-type and HBV-Tg mice. The administration of HBsAg, cGAMP, and SPD increased serum HBsAb levels in wild-type and HBV-Tg mice. In HBV-Tg mice, the administration of SPD + cGAMP or SPD + K3-SPG with HBV vaccination significantly reduced HBsAg levels in the liver and serum.

Conclusions:

These results indicate that the combination of HBV vaccine adjuvant and SPD induces a stronger humoral and cellular immune response through T-cell activation. These treatments may support the development of a strategy to completely eliminate HBV.
Liver organoids: established tools for disease modeling and drug development
Authors: Sun Xi-Cheng , Kong De-fu , Zhao Jie , Faber Klaas Nico , Xia Qiang , He Kang
Published: March 2023

In the past decade, liver organoids have evolved rapidly as valuable research tools, providing novel insights into almost all types of liver diseases, including monogenic liver diseases, alcohol-associated liver disease, metabolic-associated fatty liver disease, various types of (viral) hepatitis, and liver cancers. Liver organoids in part mimic the microphysiology of the human liver and fill a gap in high-fidelity liver disease models to a certain extent. They hold great promise to elucidate the pathogenic mechanism of a diversity of liver diseases and play a crucial role in drug development. Moreover, it is challenging but opportunistic to apply liver organoids for tailored therapies of various liver diseases. The establishment, applications, and challenges of different types of liver organoids, for example, derived from embryonic, adult, or induced pluripotent stem cells, to model different liver diseases, are presented in this review.
A nomogram for preoperative prediction of microvascular invasion in ruptured hepatocellular carcinoma
Authors: Xia Feng , Zhang Qiao , Ndhlovu Elijah , Zheng Jun , Gao Hengyi , Xia Guobing
Published: March 2023

Background and aim

Microvascular invasion (MVI) is defined as the presence of micrometastatic cancer cell emboli in hepatic vessels, including small vessels, and at present, researchers believe that is an important factor for early postoperative recurrence and survival. Here, we developed and validated a preoperative predictive model for the presence of MVI in patients with ruptured hepatocellular carcinoma (rHCC).

Methods

We retrospectively collected data for 210 rHCC patients who underwent staged hepatectomy at Wuhan Tongji Hospital, and 91 patients who underwent staged hepatectomy at Zhongshan People’s Hospital between January 2010 and March 2021. Then, the former was used as the training cohort and the latter was used as the validation cohort. Logistic regression was used to screen for variables associated with MVI, and these variables were used to construct nomograms. We used R software to assess the discrimination, calibration ability, as well as clinical efficacy of nomograms.

Results

Multivariate logistic regression analysis identified four risk factors independently associated with MVI: max tumor length [odds ratio (OR) = 1.385; 95% confidence interval (CI), 1.072–1.790], number of tumors (OR = 2.182; 95% CI, 1.129–5.546), direct bilirubin (OR = 1.515; 95% CI, 1.189–1.930), and alpha-fetoprotein (cutoff = 400 ng/mL) (OR = 2.689; 95% CI, 3.395–13.547). Nomograms were built from the four variables and they were tested for discrimination and calibration, and the results were good.

Conclusion

We developed and validated a preoperative predictive model for the presence of MVI in patients with ruptured HCC. This model can help clinicians identify patients at risk of MVI and make better treatment options.
Navigating the Storm
Authors: Landreth Sara , Pridgeon Sean , Ge Bin , Craig Kevin , Scott Susan D.
Published: March 2023

Nominal research illustrates the lived experience of intensive care unit registered nurses during the COVID pandemic. Palliative care team leaders and nurse researchers designed this cross-sectional study to discover opportunities for palliative care team members to enhance the experience of nurses who cared for critically ill patients during this challenging time. The study aimed to compare the effect of caring for patients in COVID versus non-COVID units. Surveys were distributed after the area's initial COVID patient influx. Questions included general demographics, the Professional Quality of Life survey instrument (measuring compassion satisfaction, burnout, and secondary traumatic stress), and open-ended questions to identify protective factors and unique challenges. Across 5 care settings with 311 nurses eligible for the study in total, 90 completed the survey. The population consisted of COVID-designated unit nurses (n = 48, 53.33%) and non-COVID unit nurses (n = 42, 46.67%). Analysis between COVID-designated and non-COVID units revealed significantly lower mean compassion scores and significantly higher burnout and stress scores among those working within COVID-designated units. Despite higher levels of burnout and stress and lower levels of compassion, nurses identified protective factors that improved coping and described challenges they encountered. Palliative care clinicians used insights to design interventions to mitigate identified challenges and stressors.
Nissen Versus Toupet Fundoplication For Gastro-oesophageal Reflux Disease, Short And Long-term Outcomes. A Systematic Review And Meta-analysis
Authors: Salman Mohamed AbdAlla , Salman Ahmed , Shaaban Hossam El-Din , Alasmar Mohamed , Tourky Mohamed , Elhaj Mujahid Gasemelseed Fadlallah , Khalid Sadaf , Gebril Mahmoud , Alrahawy Mahmoud , Elsherbiney Mohammed , Assal Mohamed Moustafa , Osman Mohamed Hosny Abdo , Mohammed Aboalgasim Alamin , Elewa Ahmed
Published: March 2023

Background:

Gastroesophageal reflux disease (GERD) remains one of the most commonly encountered gastrointestinal disorders. Proton pump inhibitors still show an inadequate effect on about 10% to 40% of the patients. Laparoscopic antireflux surgery is the surgical alternative for managing GERD in patients who are not responding to proton pump inhibitors.

Aim of the Study:

This study objected at comparing laparoscopic Nissen fundoplication and laparoscopic Toupet fundoplication (LTF) concerning the short-term and long-term outcomes.

Patients and Methods:

This is a systematic review and meta-analysis that evaluated the studies comparing between Nissen fundoplication and LTF for the treatment of GERD. Studies were obtained by searching on the EMBASE, the Cochrane Central Register of Controlled Trials, and PubMed central database

Results:

The LTF group showed significantly longer operation time, less postoperative dysphagia and gas bloating, less pressure on the lower esophageal sphincter, and higher Demeester scores. No statistically significant differences were found between the 2 groups in the perioperative complications, the recurrence of GERD, the reoperation rate, the quality of life, or the reoperation rate.

Conclusion:

LTF is favored for the surgical treatment of GERD being of lower postoperative dysphagia and gas bloating rates. These benefits were not at the expense of significantly additional perioperative complications or surgery failure.
Prevalence and Bother of Postvoid Dribbling and Urine Spraying or Splitting: Survey of a General Gynecology Population
Authors: Hicks Christina , Hare Adam M. , Pruszynski Jessica E. , Rahn David D.
Published: March 2023

Importance

Postvoid dribbling is described well for men in urologic literature but is poorly defined for women, especially in those not presenting for urogynecologic care.

Objective

The objective was to assess prevalence and bother of postvoid dribbling, urine spraying (ie, deviation of the urine stream), and other bothersome voiding/storage symptoms in a general gynecology population.

Study Design

This was an anonymous cross-sectional survey study of women presenting to academic general gynecology practices for benign gynecologic care or well-woman visits; patients were not presenting for urinary incontinence or voiding dysfunction. A questionnaire was used to assess the presence and perceptions of voiding behavior and urinary symptoms with an emphasis on postvoid dribbling and urine spraying. The questionnaire included both the validated Questionnaire for Urinary Incontinence Diagnosis and nonvalidated questions.

Results

Nonpregnant adult women (N = 355) were surveyed. The median age was 43 years (interquartile range, 33–51 years). The sample was 45% White, 23% Black, 3% Asian, and 13% other. Furthermore, 39% were Latina; 68%, parous; and 28%, postmenopausal. The prevalence (95% confidence interval) of immediate postvoid dribbling was 186 of 327 or 57% (51–62%), and of these, it was at least somewhat bothersome in 37% but moderately-to-quite-a-bit bothersome in 8%. Urine spraying occurred in 222 of 333 or 67% (61–72%), and of these, it was at least somewhat bothersome in 53% but moderately-to-quite-a-bit bothersome in 17%. Approximately 20% reported stress and/or urgency urinary incontinence; both postvoid dribbling and urine spraying were highly associated with these symptoms.

Conclusions

This study of women seeking benign gynecologic care shows a high prevalence of postvoid dribbling and urine spraying symptoms. However, moderate-or-greater bother was relatively uncommon.
Bayesian cluster analysis
Authors: Wade S.
Published: March 2023

Bayesian cluster analysis offers substantial benefits over algorithmic approaches by providing not only point estimates but also uncertainty in the clustering structure and patterns within each cluster. An overview of Bayesian cluster analysis is provided, including both model-based and loss-based approaches, along with a discussion on the importance of the kernel or loss selected and prior specification. Advantages are demonstrated in an application to cluster cells and discover latent cell types in single-cell RNA sequencing data to study embryonic cellular development. Lastly, we focus on the ongoing debate between finite and infinite mixtures in a model-based approach and robustness to model misspecification. While much of the debate and asymptotic theory focuses on the marginal posterior of the number of clusters, we empirically show that quite a different behaviour is obtained when estimating the full clustering structure.

This article is part of the theme issue ‘Bayesian inference: challenges, perspectives, and prospects’.
On free energy barriers in Gaussian priors and failure of cold start MCMC for high-dimensional unimodal distributions
Authors: Bandeira Afonso S. , Maillard Antoine , Nickl Richard , Wang Sven
Published: March 2023

We exhibit examples of high-dimensional unimodal posterior distributions arising in nonlinear regression models with Gaussian process priors for which Markov chain Monte Carlo (MCMC) methods can take an exponential run-time to enter the regions where the bulk of the posterior measure concentrates. Our results apply to worst-case initialized (‘cold start’) algorithms that are local in the sense that their step sizes cannot be too large on average. The counter-examples hold for general MCMC schemes based on gradient or random walk steps, and the theory is illustrated for Metropolis–Hastings adjusted methods such as preconditioned Crank–Nicolson and Metropolis-adjusted Langevin algorithm.

This article is part of the theme issue ‘Bayesian inference: challenges, perspectives, and prospects’.
Determining the impact of vaccination on SARS-CoV-2 RT-PCR cycle threshold values and infectious viral titers
Authors: Peterson Katherine L , Snyder Julia P , Despres Hannah W , Schmidt Madaline M , Eckstrom Korin M , Unger Allison L , Carmolli Marya P , Sevigny Joseph L , Shirley David J , Dragon Julie A , Thomas W. Kelley , Bruce Emily A , Crothers Jessica W
Published: March 2023

ABSTRACT
Background: As the COVID-19 pandemic continues, efforts to better understand SARS-CoV-2 viral shedding and transmission in both unvaccinated and vaccinated populations remain critical to informing public health policies and vaccine development. The utility of using RT-PCR cycle threshold values (CT values) as a proxy for infectious viral titers from individuals infected with SARS-CoV-2 is yet to be fully understood. This retrospective observational cohort study compares quantitative infectious viral titers derived from a focus-forming viral titer assay with SARS-CoV-2 RT-PCR CT values in both unvaccinated and vaccinated individuals infected with the Delta strain.
Methods: Nasopharyngeal swabs positive for SARS-CoV-2 by RT-PCR with a CT value < 27 collected from June 26th to October 17th of 2021 at the University of Vermont Medical Center Clinical Laboratory for which vaccination records were available were included. Partially vaccinated and individuals < 18 years of age were excluded. Infectious viral titers were determined using a micro-focus forming assay under BSL-3 containment.
Results: 119 specimens from 22 unvaccinated and 97 vaccinated individuals met all inclusion criteria and had sufficient residual volume to undergo viral titering. A negative correlation between RT-PCR CT values and viral titers was observed in both unvaccinated and vaccinated groups. No difference in mean CT value or viral titer was detected between vaccinated and unvaccinated groups. Viral titers did not change as a function of time since vaccination.
Conclusions: Our results add to the growing body of knowledge regarding the correlation of SARS-CoV-2 RNA levels and levels of infectious virus. At similar CT values, vaccination does not appear to impact an individual’s potential infectivity.
In situ Patch-seq analysis of microglia reveals a lack of stress genes as found in FACS-isolated microglia
Authors: Bakina Olga , Conrad Thomas , Mitic Nina , Vidal Ramon Oliveira , Obrusnik Tessa , Sai Somesh , Nolte Christiane , Semtner Marcus , Kettenmann Helmut
Published: March 2023

We applied the patch-seq technique to harvest transcripts from individual microglial cells from cortex, hippocampus and corpus callosum of acute brain slices from adult mice. After recording membrane currents with the patch-clamp technique, the cytoplasm was collected via the pipette and underwent adapted SMART-seq2 preparation with subsequent sequencing. On average, 4138 genes were detected in 113 cells from hippocampus, corpus callosum and cortex, including microglia markers such asTmem119, P2ry12andSiglec-H. Comparing our dataset to previously published single cell mRNA sequencing data from FACS-isolated microglia indicated that two clusters of cells were absent in our patch-seq dataset. Pathway analysis of marker genes in FACS-specific clusters revealed association with microglial activation and stress response. This indicates that under normal conditions microgliain situlack transcripts associated with a stress-response, and that the microglia-isolation procedure by mechanical dissociation and FACS triggers the expression of genes related to activation and stress.
Evolution of a Functionally Intact but Antigenically Distinct DENV Fusion Loop
Authors: Meganck Rita M. , Zhu Deanna , Dong Stephanie , Snoderly-Foster Lisa J. , Dalben Yago R. , Thiono Devina , White Laura J. , DeSilva Aravinda M. , Baric Ralph S. , Tse Longping V.
Published: March 2023

A hallmark of Dengue virus (DENV) pathogenesis is the potential for antibody-dependent enhancement, which is associated with deadly DENV secondary infection, complicates the identification of correlates of protection, and negatively impacts the safety and efficacy of DENV vaccines. ADE is linked to antibodies targeting the fusion loop (FL) motif of the envelope protein, which is completely conserved in mosquito-borne flaviviruses and required for viral entry and fusion. In the current study, we utilized saturation mutagenesis and directed evolution to engineer a functional variant with a mutated FL (D2-FL) which is not neutralized by FL-targeting monoclonal antibodies. The FL mutations were combined with our previously evolved prM cleavage site to create a mature version of D2-FL (D2-FLM), which evades both prM- and FL-Abs but retains sensitivity to other type-specific and quaternary cross-reactive (CR) Abs. CR serum from heterotypic (DENV4) infected non-human primates (NHP) showed lower neutralization titers against D2-FL and D2-FLM than isogenic wildtype DENV2 while similar neutralization titers were observed in serum from homotypic (DENV2) infected NHP. We propose D2-FL and D2-FLM as valuable tools to delineate CR Ab subtypes in serum as well as an exciting platform for safer live attenuated DENV vaccines suitable for naïve individuals and children.
Dominant negative OTULIN Related Autoinflammatory Syndrome
Authors: Davidson Sophia , Shibata Yuri , Collard Sophie , Laohamonthonku Pawat , Kong Klara , Sun June ,   CIRCA,   AADRY, Li Margaret W.Y. , Russell Carolyn , van Beek Anna , Kirk Edwin P , Walsh Revecca , Gray Paul E , Komander David , Masters Seth L
Published: March 2023

Biallelic loss of function mutations in the linear chain specific deubiquitinase (DUB) OTULIN (OTU Deubiquitinase With Linear Linkage Specificity) result in OTULIN Related Autoinflammatory Syndrome (ORAS). To date all reported ORAS patients have had homozygous or compound heterozygous loss of function mutations, however we identified a patient with a monoallelic heterozygous mutation p.Cys129Ser. Consistent with the ORAS phenotype, we observed accumulation of linear ubiquitin chains, increased sensitivity to TNF induced cell death and dysregulation of inflammatory signalling in both patient cells and in vitro exogenous expression models. Levels of the mutant OTULIN protein were consistent with wild type OTULIN in patient cells and exogenous expression systems and maintained binding capacity to both LUBAC and linear ubiquitin chains. However, even in a heterozygous context this mutant DUB promoted the global accumulation of linear ubiquitin chains. Furthermore, it allowed accumulation of ubiquitin on the linear ubiquitin chain assembly complex (LUBAC). Altered ubiquitination of LUBAC leads to a dysregulation of NF-κB signalling and promotion of TNF induced cell death. By reporting the first dominant negative mutation driving ORAS this study expands our clinical understanding of Otulin mediated pathology.
A gene network implicated in the joint-muscle pain, brain fog, chronic fatigue, and bowel irregularity of Ehlers-Danlos and “long” COVID19 syndromes
Authors: Wilson Golder N.
Published: March 2023

Objectives

Characterization of tissue laxityanddysautonomia symptoms in Ehlers-Danlos syndrome (EDS) uncovered similarities with those of post-infectious SARS-CoV-2 or long COVID19, prompting detailed comparison of their findings and influencing genes.

Methods

Holistic assessment of 1261 EDS outpatients for 120 history-physical findings populated a deidentified database that includes 568 patients with 317 variant genes obtained by commercial NextGen sequencing. Findings were compared to 15 of long COVID19 compiled in an extensive review, genes to 104 associated with COVID19 severity in multiple molecular studies.

Results

Fifteen symptoms common to Ehlers-Danlos versus long COVID19 ranged from brain fog (27-80 versus 30-70%), chronic fatigue (38-91; 30-60%), dyspnea (32-52; 29-52%) to irritable bowel (67-89; 14-78%), muscle weakness (22-49; 15-25%), and arthritis (32-94; 15-27%). Genes relevant to EDS included 6 identical to those influencing COVID19 severity (F2,LIFR,NLRP3,STAT1,T1CAM1,TNFRSF13B) and 18 similar includingPOLG-POLD4,SLC6A2-SLC6A20, andNFKB1-NFKB2. Both gene sets had broad genomic distribution, many mitochondrial genes influencing EDS and many involved with immunity-inflammation modifying COVID19 severity. Recurring DNA variants in EDS that merit evaluation in COVID19 resistance include those impacting connective tissue elements--51 inCOL5(joint), 29 inCOL1/2/9/11(bone), 13 inCOL3(vessel), and 18 inFBN1(vessel-heart)--or neural function--93 in mitochondrial DNA, 28 inCOL6/12, 16 inSCN9A/10A/11A, 14 inPOLG, and 11 in genes associated with porphyria.

Conclusions

Holistic ascertainment of finding pattern and exome variation in EDS defined tissue laxity, neuromuscular, and autonomic correlations that transcend single abnormalities or types. Implied networks of nuclear and mitochondrial genes are linked to findings like brain fog, fatigue, and frailty in EDS, their similarity to long COVID19 supporting shared therapies for disorders affecting a minimum 0.1% of the global population.
Quantification of measurable residual disease using duplex sequencing in adults with acute myeloid leukemia
Authors: Dillon Laura W. , Higgins Jake , Nasif Hassan , Othus Megan , Beppu Lan , Smith Thomas H. , Schmidt Elizabeth , Valentine Charles C. , Salk Jesse J. , Wood Brent L , Erba Harry P. , Radich Jerald P. , Hourigan Christopher S.
Published: March 2023

The presence of measurable residual disease (MRD) is strongly associated with treatment outcomes in acute myeloid leukemia (AML). Despite the correlation with clinical outcomes, MRD assessment has yet to be standardized or routinely incorporated into clinical trials. Discrepancies have been observed between different techniques for MRD assessment and there remains a need to compare centralized, high-quality multiparametric flow cytometry (MFC) and ultrasensitive next-generation sequencing (NGS) in AML patients with diverse mutational profiles. In 62 patients with AML, aged 18-60, in first complete remission after intensive induction therapy on the randomized phase 3 SWOG-S0106 clinical trial, MRD detection by MFC was compared with a 29 gene panel utilizing duplex sequencing (DS), an NGS method that generates double-stranded consensus sequences to reduce false positive errors. Using DS, detection of a persistent mutation utilizing defined criteria was seen in 22 (35%) patients and was strongly associated with higher rates of relapse (68% vs 13% at year 5; HR, 8.8; 95% CI, 3.2-24.5; P<0.001) and decreased survival (32% vs 82% at year 5; HR, 5.6; 95% CI, 2.3-13.8; P<0.001). MRD as defined by DS strongly outperformed MFC, which was observed in 10 (16%) patients and marginally associated with higher rates of relapse (50% vs 30% at year 5; HR, 2.4; 95% CI, 0.9-6.7; P=0.087) and decreased survival (40% vs 68% at year 5; HR, 2.5; 95% CI, 1.0-6.3; P=0.059). Furthermore, the prognostic significance of DS MRD status at the time of remission was similar on both randomized arms of the trial, predicting S0106 clinical trial outcomes. These findings suggest that DS is a powerful tool that could be used in patient management and for early treatment assessment in clinical trials.
Siglecs in the Porcine Oviduct and Sialylated Ligands on Sperm: Roles in the Formation of the Sperm Reservoir
Authors: Molina Leonardo M. , Pepi Lauren E. , Shajahan Asif , Doungkamchan Kankanit , Azadi Parastoo , McKim Daniel B. , Miller David J.
Published: March 2023

Abstract

During mammalian insemination, most of the deposited sperm are lost by retrograde flow or the female reproductive tract’s immune response. Once semen enters the uterus, seminal fluid and sperm elicit leukocyte infiltration that contributes to the elimination of sperm in the uterus. However, unlike the uterus, invading sperm do not trigger a phagocytic response in the oviduct in the absence of dysfunction or disease states. Thus, the oviduct possesses a distinct immunological microenvironment that tolerates sperm while maintaining the capacity to respond to pathogens. It has been suggested that sperm glycocalyx contributes to innate oviductal tolerance, but the cell and molecular mechanisms are not understood. The current investigation focused on the role of sialic acid-containing glycoconjugates on sperm and their potential to elicit innate tolerance via cognate sialic acid-binding immunoglobulin-type lectins (Siglecs) expressed in the oviduct. In this manuscript, we report our discovery of eight Siglecs (Siglecs-1, -2, -3, -5, -10, -11, -14, -15) expressed in the lower pig oviduct, five of which are known for immune inhibitory functions (Siglecs-2, -3, -5, -10, and -11) and how these may play a role in achieving sperm-induced immune suppression in the oviduct microenvironment. Mass spectrometry profiling of porcine sperm revealed the presence of a mixture of α2,3 and α2,6 linked sialic acids with α2,3-linked sialic acids as the dominant linkage. Of the detected glycans, several sialic acid-containing glycoconjugates were identified as potential ligands for Siglecs (among O-linked glycans: NeuAc1GalNAc1, NeuGc1GalNAc1, NeuAc2Gal1GalNAc1; attached to glycolipids: NeuAc2Gal1GalNAc1Gal1Glc1, Fuc1Gal1GalNAc1NeuAc1Gal1Glc1). This is the first report of Siglec expression in the mammalian oviduct and total glycan analysis of porcine sperm. The results of this study reveal the potential for a sperm-sialoglycan and oviductal-Siglec axis that may contribute to the distinct immunophysiology of the oviduct fundamentally required for undisrupted reproduction in mammals.
An efficient, scarless, selection-free technology for phage engineering
Authors: Goren Moran G , Mahata Tridib , Qimron Udi
Published: March 2023

Many phage engineering technologies, mainly based on the CRISPR-Cas system, have been recently developed. Here we present a method to genetically engineer theEscherichia coliphages T5, T7, and P1 by adapting a technology, called pORTMAGE, developed for engineering bacterial genomes. The technology comprises ofE. coliharboring a plasmid encoding a potent recombinase and a gene transiently silencing a repair system. Oligonucleotides with the desired phage mutation are electroporated intoE. colifollowed by infection of the target bacteriophage. The high efficiency of this technology, ranging from 1-14% of desired recombinants, allows low-throughput screening for the desired mutant. We demonstrated the use of this technology for single-base substitutions, for deletions of 50 bases, for insertions of 20 bases, and for three different phages. The technology may be adjusted for use across many bacterial and phage strains.
Dual stop codon suppression in mammalian cells with genomically integrated genetic code expansion machinery
Authors: Meineke Birthe , Heimgärtner Johannes , Caridha Rozina , Block Matthias F , Kimler Kyle J , Pires Maria F , Landreh Michael , Elsässer Simon J
Published: March 2023

Genetic code expansion via stop codon suppression is a powerful strategy to engineer proteins. Pyrrolysyine-tRNA (tRNAPyl)/pyrrolysyl-tRNA synthetase (PylRS) pairs from methanogenic archaea and engineered bacterial tRNA/aminoacyl-tRNA synthetases (aaRS) pairs are used for site-specific incorporation of noncanonical amino acids (ncAAs) in response to stop codons in mammalian cells. Routinely, ncAA incorporation is achieved by transient expression of the tRNA/aaRS pair leading to heterogeneous suppression. Genomic integration of tRNA/aaRS expression cassettes for more homogenous, adjustable and reproducible levels of protein, containing one or more ncAA, will greatly benefit protein engineering, chemical control and imaging applications in mammalian cells. Here, we demonstrate that piggyBac-mediated genomic integration of archaeal tRNAPyl/PylRS or bacterial tRNA/aaRS pairs, using a modular plasmid design with multi-copy tRNA arrays, allows for homogeneous and efficient, genetically encoded ncAA incorporation in diverse mammalian cell lines. We assess opportunities and limitations of using ncAAs for fluorescent labeling applications in stable cell lines. We explore simultaneous suppression of ochre and opal stop codons and finally incorporate two distinct ncAAs with mutually orthogonal click chemistries for site-specific, dual fluorophore labeling of a cell surface receptor on live mammalian cells.
The mitotic surveillance pathway requires PLK1-dependent 53BP1 displacement from kinetochores
Authors: Burigotto Matteo , Vigorito Vincenza , Mattivi Alessia , Gliech Colin , Ghetti Sabrina , Bisio Alessandra , Lolli Graziano , Holland Andrew J. , Fava Luca L.
Published: March 2023

53BP1 acts at the crossroads between DNA repair and p53-mediated stress response. With its interactor USP28, it is part of the mitotic surveillance pathway (MSP), a sensor that monitors the duration of cell division, promoting p53-dependent cell cycle arrest when a critical time threshold is surpassed. 53BP1 dynamically associates with kinetochores, being recruited during prophase, and then undergoing a time-dependent loss of affinity. However, the relevance of this behaviour remains unclear. Here, we identify CENP-F as an interaction partner and kinetochore receptor for 53BP1. By engineering human cells with a CENP-F point mutation, we demonstrate that preventing 53BP1 kinetochore localization does not reduce MSP proficiency. Strikingly, however, preventing the loss of 53BP1 from the kinetochore by inhibiting Polo-like kinase 1 (PLK1) restrains MSP activity, a phenomenon that is abrogated in the CENP-F mutant condition. Taken together, we demonstrate that kinetochore-loaded 53BP1 represents an MSP functionally inhibited state and that PLK1-dependent re-localization of 53BP1 represents an important layer of MSP regulation.
CSR, monitoring cost and firm performance during COVID-19: balancing organizational legitimacy and agency cost
Authors: Yadav Sandeep , Srivastava Jagriti
Published: March 2023

Purpose

COVID-19 induced uncertainty in the firms’ business transactions, financial markets and product-market competition, causing a severe organizational legitimacy crisis. Using the organizational legitimacy perspective and agency theory, this paper aims to study the relationship between prior corporate social responsibility (CSR) activities, monitoring cost (MC) and firm performance.

Design/methodology/approach

This study uses a quarterly panel (16,924 firm-quarter observations from 61 countries for CSR and 53,345 firm-quarter observations from 55 countries for MC) for 14 quarters from January 2018 to June 2021. This study uses panel fixed-effect regression models to estimate the effect of CSR activities and MC (measured as audit fees) on firm performance during the COVID-19 period.

Findings

This study finds a U-shaped relationship between CSR and firm performance. This relationship is strengthened during COVID-19. In contrast, this study finds an inverted U-shaped relationship between firm MC and firm performance. However, this relationship is weakened during the pandemic.

Originality/value

This study contributes to theory and practice on maintaining organizational legitimacy and reducing agency costs during the pandemic. This study shows that firms’ prior legitimacy-gaining practices, such as CSR activities and MC, provide an opportunity to increase firm value. To balance agency costs and legitimacy benefits, firm managers also need to identify the optimal level of CSR activities and MC.
A longitudinal study investigating changing implicit leadership theory in an Irish business school
Authors: Berkery Elaine , Ryan Nuala F.
Published: March 2023

Purpose

The purpose of this study is to investigate changing implicit leadership theories (ILTs) within a business student population over a ten-year period.

Design/methodology/approach

Students from the same business student population rated men, women and managers in general, using Schein’s Descriptive Index, first during the academic year 2008–2009 and again in 2018–2019.

Findings

In Sample 1, the authors found multiple ILTs, male students gender typed the managerial role in favour of men, while female students held a more gender egalitarian view of the managerial role. In Sample 2, the authors found evidence that ILTs are starting to converge, as neither the male nor female sample gender typed the managerial role.

Practical implications

These results aid the understanding of the ILTs that these graduating professionals bring into their new full-time organisations.

Originality/value

The analysis of data from the same population using the same measurement at ten-year intervals, along with the findings that male students no longer gender type the managerial role in the most recent round of data collection, are original contributions to the literature.
Text classification in tourism and hospitality – a deep learning perspective
Authors: Liu Jun , Hu Sike , Mehraliyev Fuad , Liu Haolong
Published: March 2023

Purpose

This study aims to investigate the current state of research using deep learning methods for text classification in the tourism and hospitality field and to propose specific guidelines for future research.

Design/methodology/approach

This study undertakes a qualitative and critical review of studies that use deep learning methods for text classification in research fields of tourism and hospitality and computer science. The data was collected from the Web of Science database and included studies published until February 2022.

Findings

Findings show that current research has mainly focused on text feature classification, text rating classification and text sentiment classification. Most of the deep learning methods used are relatively old, proposed in the 20th century, including feed-forward neural networks and artificial neural networks, among others. Deep learning algorithms proposed in recent years in the field of computer science with better classification performance have not been introduced to tourism and hospitality for large-scale dissemination and use. In addition, most of the data the studies used were from publicly available rating data sets; only two studies manually annotated data collected from online tourism websites.

Practical implications

The applications of deep learning algorithms and data in the tourism and hospitality field are discussed, laying the foundation for future text mining research. The findings also hold implications for managers regarding the use of deep learning in tourism and hospitality. Researchers and practitioners can use methodological frameworks and recommendations proposed in this study to perform more effective classifications such as for quality assessment or service feature extraction purposes.

Originality/value

The paper provides an integrative review of research in text classification using deep learning methods in the tourism and hospitality field, points out newer deep learning methods that are suitable for classification and identifies how to develop different annotated data sets applicable to the field. Furthermore, foundations and directions for future text classification research are set.
Exploring crucial social media marketing factors for improving customer satisfaction and customer loyalty in bed and breakfast sectors in Taiwan
Authors: Nalluri Venkateswarlu , Yang Kai-Fu , Chen Long-Sheng , Yang Tzung-Yu Kevin
Published: March 2023

Purpose

The Bed and Breakfast (B&B) enterprises generally lack sufficient human resources and time to conduct research on important social media marketing factors for visitors’ satisfaction and visitors’ intentions. Therefore, this study aims to provide crucial social media marketing and factors and service quality elements for improving customer satisfaction and customer loyalty in B&B sectors. This study also provides some recommendations for attracting more visitors and increasing customer satisfaction and customer loyalty through social media.

Design/methodology/approach

First, social media marketing factors and service quality elements were identified through the systematic literature review. Then these identified factors and elements were used to design a survey questionnaire for collecting data. The research data included responses of 64 B&B enterprises and 625 customers. The collected data was analyzed by feature selection approaches including Decision Tree algorithm and Information Gain to identify the key factors for improving customer satisfaction and customer loyalty.

Findings

The findings of this study determined that featured choice is an important social media marketing factor, and assurance is the common service quality element for both B&B enterprises and their customers in terms of satisfaction and loyalty.

Originality/value

This study adds a value to the growing literature on customer satisfaction and loyalty in B&B sectors by exploring key social media marketing factors and service quality elements. The study reveals several implications for theories and practices. The findings hopefully help B&B enterprises better social media marketing with less workforce and budget.
Enhance pick-and-place performance using multimodal interaction in operation environment
Authors: Guo Xinwei , Chen Yang
Published: March 2023

Purpose

Currently, the vision and depth information obtained from the eye-to-hand RGB-D camera can apply to the reconstruction of the three-dimensional (3D) environment for a robotic operation workspace. The reconstructed 3D space contributes to a symmetrical and equal observation view for robots and humans, which can be considered a digital twin (DT) environment. The purpose of this study is to enhance the robot skill in the physical workspace, although the artificial intelligence (AI) technique has high performance of the robotic operation in the known environments.

Design/methodology/approach

A multimodal interaction framework is proposed in DT operation environments.

Findings

A fast image-based target segmentation technique is combined in the 3D reconstruction of the robotic operation environment from the eye-to-hand camera, thus expediting the 3D DT environment generation without accuracy loss. A multimodal interaction interface is integrated into the DT environment.

Originality/value

The users are supported to operate the virtual objects in the DT environment using speech, mouse and keyboard simultaneously. The humans’ operations in 3D DT virtual space are recorded, and cues are provided for the robot’s operations in practice.
Impact of US-China trade war on Asian economies: neural network multilayer perceptron approach
Authors: Rahman Mohd Nayyer , Iqbal Badar Alam , Rahman Nida
Published: March 2023

Purpose

This study aims to find the impact of the trade war between the USA and China on Asian economies. Apart from macroeconomic variables associated with trade, this study explicitly creates a trade war scenario and trade war participant dummies. Using the neural network multilayer perceptron, this study checks for the causal linkages between the predictors and target output for the panel of Asian economies and the USA.

Design/methodology/approach

A conceptual model of the after effects of trade war in a quadrant is developed. Variables related to trade and tariffs are included in the study for a panel of 19 Asian economies. The feedforward structure of neural network analysis is used to identify strong and weak predictors of trade war.

Findings

The hidden layers of the multilayer perceptron reveal the inconsistency in linkages for the predictors’ services exports, tariff measures, anti-dumping measures, trade war scenario dummy with gross domestic product. The findings suggest that to curtail the impact of the trade war on Asian economies, predictors with neural evidence must be paid due weightage in policy determination and trade agreements.

Originality/value

The study applies a novel and little explored AI/ML technique of Neural Network analysis with training of 70% observations. The paper will provide opportunity for other researchers to explore techniques of AI/ML in trade studies.