bluuebunny/crossref_metadata_2025 huggingface dataset:
Establishing a Quality Improvement Program for Pediatric In-hospital Cardiac Arrest
Authors: Freedman Anya J. , Madsen Erik C. , Lowrie Lia
Published: December 2023

Background:

Pediatric In-hospital Cardiac Arrest (IHCA) is a rare event with a 50-55% mortality rate. Techniques of Cardiopulmonary Resuscitation (CPR), medication and electrical therapy timing, team dynamics, simulation and debriefing programs are associated with improved outcomes. This study aimed to improve outcomes after IHCA by describing and implementing quality improvement processes that cross and coordinate among traditional siloed pediatric resuscitation team structures.

Methods:

We chose three outcome measures: (1) return of spontaneous circulation (ROSC), (2) 24-hour survival after IHCA, and (3) survival to hospital discharge. Process outcomes include (1) hot debriefs performed with a standardized form, (2) code documentation using a revised form, and (3) formal code team review presented to a central Emergency Management Committee, using a standardized form.

Results:

One hundred and thirty-two patients experienced 176 events during the 36-month study period. Survival to hospital discharge increased from 33% during year 1 to 60% during year 2 (P < 0.05) but decreased to 45% in year 3. Both hot debrief performance and code documentation process methods did not demonstrate widespread adoption, but formal code team review was documented in 80% of events quite rapidly.

Conclusions:

There are common traits inherent to effective CPR team response. Ensuring optimal performance of these common tasks and techniques in every pediatric IHCA event in our hospital is being addressed by committee reorganization, task simplification, new technology acquisition and enhanced feedback loops. Early outcome analysis shows initial improvement in survival to hospital discharge after pediatric IHCA.
Improving Pediatric Ovarian Torsion Evaluation in the Pediatric Emergency Department: A Quality Improvement Initiative
Authors: Park Brian L. , Fenstermacher Sara , Stanescu A. Luana , Rutman Lori , Kinneman Lauren , Solari Patrick
Published: December 2023

Background:

Transabdominal pelvic ultrasound (TPUS) is the diagnostic test of choice for the evaluation of ovarian torsion, a time-sensitive surgical emergency. A full bladder is required to visualize the ovaries. Bladder filling is a time-consuming process leading to delays to TPUS, poor visualization of ovaries requiring repeat studies, and prolonged emergency department length of stay (ED LOS). The primary objective was to decrease the time to TPUS by standardizing the bladder filling process.

Methods:

This quality improvement initiative occurred at a single, academic, quaternary-care children’s hospital ED and utilized the Institute for Healthcare Improvement Model for Improvement with sequential plan-do-study-act cycles. The first set of interventions implemented in August 2021 included a new electronic order set and bladder scan by ED nurses. Subsequent plan-do-study-act cycles aimed to decrease the time to intravenous fluid, decrease fluid requirement, and decrease the need for intravenous fluid. The primary outcome measure was the monthly mean time to TPUS. Secondary outcome measures included monthly mean ED LOS and percentage of repeat TPUS. We performed data analysis with statistical process control charts to assess for system change over time.

Results:

The preintervention baseline included 292 ED encounters more than 10 months, and postintervention analysis included 526 ED encounters more than 16 months. Time to TPUS decreased (138–120 min), ED LOS decreased (372–335 min), and repeat TPUS decreased (18% to 4%). All changes met the rules for special cause variation.

Conclusions:

Standardizing the bladder filling process was associated with decreased time to TPUS, ED LOS, and repeat TPUS.
Nationwide Outcome after Pancreatoduodenectomy in Patients at Very High Risk (ISGPS-D) for Postoperative Pancreatic Fistula
Authors: Theijse Rutger T. , Stoop Thomas F. , Hendriks Tessa E. , Suurmeijer J. Annelie , Smits F. Jasmijn , Bonsing Bert A. , Lips Daan J. , Manusama Eric , van der Harst Erwin , Patijn Gijs A. , Wijsman Jan H. , Meerdink Mark , den Dulk Marcel , van Dam Ronald , Stommel Martijn W.J. , van Laarhoven Kees , de Wilde Roeland F. , Festen Sebastiaan , Draaisma Werner A. , Bosscha Koop , van Eijck Casper H.J. , Busch Olivier R. , Molenaar I. Quintus , Groot Koerkamp Bas , van Santvoort Hjalmar C. , Besselink Marc G. ,   for the Dutch Pancreatic Cancer Group
Published: December 2023

Objective:

To assess nationwide surgical outcome after pancreatoduodenectomy (PD) in patients at very high risk for postoperative pancreatic fistula (POPF), labeled as International Study Group for Pancreatic Surgery (ISGPS) category D.

Background:

Morbidity and mortality after ISGPS-D PD is perceived so high that a recent randomized trial advocated prophylactic total pancreatectomy (TP) as alternative aiming to lower this risk. However, current outcomes of ISGPS-D PD remain unknown as large nationwide series are lacking.

Methods:

Nationwide retrospective analysis including consecutive patients undergoing ISGPS-D PD (ie, soft texture and pancreatic duct diameter ≤3 mm), using the mandatory Dutch Pancreatic Cancer Audit (2014-2021). Primary outcome was in-hospital mortality, and secondary outcomes included major morbidity (ie, Clavien-Dindo grade ≥IIIa) and POPF (ISGPS grade B/C). The use of prophylactic TP to avoid POPF during the study period was assessed.

Results:

Overall, 1402 patients were included. In-hospital mortality was 4.1% (n=57), which decreased to 3.7% (n=20/536) in the last 2 years. Major morbidity occurred in 642 patients (45.9%) and POPF in 410 (30.0%), which corresponded with failure-to-rescue in 8.9% (n=57/642). Patients with POPF had increased rates of major morbidity (88.0% vs. 28.3%; P<0.001) and mortality (6.3% vs. 3.5%; P=0.016) compared to patients without POPF. Among 190 patients undergoing TP, prophylactic TP to prevent POPF was performed in 4 (2.1%).

Conclusions:

This nationwide series found a 4.1% in-hospital mortality after ISGPS-D PD with 45.9% major morbidity, leaving little room for improvement through prophylactic TP. Nevertheless, given the outcomes in the 30% of patients who develop POPF, future randomized trials should aim to prevent and mitigate POPF in this high-risk category.
Identification of NpdA as the protein forming the surface layer in Paracidovorax citrulli and evidence of its occurrence as a surface layer protein in diverse genera of the Betaproteobacteria and Gammaproteobacteria
Authors: Gajbhiye Shabda , Gonzales Erin D. , Toso Daniel B. , Kirk Natalie A. , Hickey William J.
Published: December 2023

Graphical abstract

Stylized cryo-electron image of two bacterial cells and an extracellular vesicle highlighting the presence of a surface layer (gold-colored structure).
Marivirga aurantiaca sp. nov., a halophilic nitrite-reducing bacterium, isolated from intertidal surface sediments
Authors: Zhang Mingxia , Zhang Yulian , Yao Qing , Yang Fan , Zhu Honghui
Published: December 2023

A novel Gram-stain-negative strain, designated S37H4T, was isolated from an intertidal surface sediment sample collected from Zhanjiang City, Guangdong province, south PR China. Cells of the strain were aerobic, non-flagellated, long rod-shaped and motile by gliding. S37H4T could grow at 4–40 °C, pH 7.0–8.5 and in 2.0–15.0 % NaCl, with optimal growth at 25–30 °C, pH 7.5 and 9.0 % NaCl, respectively. S37H4T was capable of nitrite removal under high-salt conditions, and there were three denitrification genes, nirK, norB and nosZ, in its genome. The results of phylogenetic analyses based on the 16S rRNA gene and genome sequences indicated that S37H4T represented a member of the genus

Marivirga

and formed a subclade with

Marivirga lumbricoides

JLT2000T. S37H4T showed the highest 16S rRNA sequence similarity to

M. lumbricoides

JLT2000T (98.3 %) and less than 97.0 % similarity with other type strains of species of the genus

Marivirga

. The average nucleotide identity (ANI) and digital DNA–DNA hybridization (dDDH) values between S37H4T and the reference type strains of species of the genus

Marivirga

were 70.7–74.3 % and 18.2–19.2 %, respectively. The major fatty acids of S37H4T were iso-C15 : 0, iso-C15 : 1G, iso-C17 : 0 3-OH and summed feature 3 (C16 : 1ω6c and/or C16 : 1ω7c). The major respiratory quinone of this novel strain was MK-7, and the predominant polar lipids were identified as phosphatidylethanolamine, an unidentified aminolipid, an unidentified phospholipid and three unidentified lipids. The results of analyses of phylogenetic, genomic, physiological and biochemical characteristics indicated that S37H4T represented a novel species of the genus

Marivirga

, for which the name Marivirga aurantiaca sp. nov. is proposed. The type strain is S37H4T (= GDMCC 1.1866T = KACC 21922T).
Sequence reliance of aDrosophilacontext-dependent transcription factor
Authors: Hodkinson Lauren J. , Gross Julia , Schmidt Casey A. , Diaz-Saldana Pamela P. , Aoki Tsutomo , Rieder Leila E.
Published: December 2023

Despite binding similarciselements in multiple locations, a single transcription factor often performs context-dependent functions at different loci. How factors integratecissequence and genomic context is still poorly understood and has implications for off-target effects in genetic engineering. TheDrosophilacontext-dependent transcription factor CLAMP targets similar GA-richciselements on the X-chromosome and at the histone gene locus but recruits very different, loci-specific factors. We discover that CLAMP leverages information from bothciselement and local sequence to perform context-specific functions. Our observations imply the importance of other cues, including protein-protein interactions and the presence of additional cofactors.
Guggulsterone Enhances NKX3.1 Expression and Induces Apoptosis in Prostate Cancer Cells: Implications for Chemoprevention
Authors: Jain Garima , Neha  , Ranjan Prashant , Devi Chandra , Atri Aditi , Cieza-Borrella Clara , Das Parimal
Published: December 2023

Aim

Prostate cancer is a leading cause of cancer-related mortality, necessitating novel therapeutic and preventive strategies. This study aimed to investigate the anti-cancer properties of Guggulsterone (GS) on prostate cancer cells, specifically focusing on its effects on homeobox protein NKX3.1, apoptosis, and mitochondrial function.

Method

The study utilized the LNCaP prostate cancer cell line and involved cell culture, dose-response analysis, flow cytometry for apoptosis quantification, siRNA-mediated knockdown of NKX3.1, mitochondrial membrane potential assessment using TMRM staining, qRT-PCR analysis, and Western blotting. The stability of NKX3.1 mRNA and protein in response to GS was also evaluated.

Result

GS treatment induced apoptosis in LNCaP cells in a dose and time-dependent manner, with an impact on early and late-stage apoptosis. This effect was mediated, at least in part, through the upregulation of NKX3.1. GS enhanced NKX3.1 expression at both the protein and mRNA levels, even in the absence of androgens. Furthermore, GS treatment extended the half-life of NKX3.1 mRNA and protein, suggesting an effect on their stability.

Conclusion

This study provides valuable insights into the anti-cancer mechanisms of GS in prostate cancer cells. The upregulation of NKX3.1 by GS and its role in mediating apoptosis offers NKX3.1 as a potential prevention target for PCa. The findings open new research avenues for the development of targeted therapies that stabilize NKX3.1 expression and protect mitochondrial function. Further investigations are needed to understand the intricate molecular mechanisms underlying GS’s effects fully, potentially improving prostate cancer management and outcomes.
An alpha- to gamma-motoneurone collateral can mitigate velocity-dependent stretch reflexes during voluntary movement: A computational study
Authors: Niyo Grace , Almofeez Lama I , Erwin Andrew , Valero-Cuevas Francisco J
Published: December 2023

The primary motor cortex does not uniquely or directly produce alpha motoneurone (α-MN) drive to muscles during voluntary movement. Rather,α-MN drive emerges from the synthesis and competition among excitatory and inhibitory inputs from multiple descending tracts, spinal interneurons, sensory inputs, and proprioceptive afferents. One such fundamental input is velocity-dependent stretch reflexes in lengthening muscles, which should be inhibited to enable voluntary movement. It remains an open question, however, the extent to which unmodulated stretch reflexes disrupt voluntary movement, and whether and how they are inhibited in limbs with numerous multi-articular muscles. We used a computational model of aRhesus Macaquearm to simulate movements with feedforwardα-MN commands only, and with added velocity-dependent stretch reflex feedback. We found that velocity-dependent stretch reflex caused movement-specific, typically large and variable disruptions to arm movements. These disruptions were greatly reduced when modulating velocity-dependent stretch reflex feedback (i) as per the commonly proposed (but yet to be clarified) idealized alpha-gamma (α-γ) co-activation or (ii) an alternativeα-MN collateral projection to homonymousγ-MNs. We conclude that suchα-MN collaterals are a physiologically tenable, but previously unrecognized, propriospinal circuit in the mammalian fusimotor system. These collaterals could still collaborate withα-γco-activation, and the few skeletofusimotor fibers (β-MNs) in mammals, to create a flexible fusimotor ecosystem to enable voluntary movement. By locally and automatically regulating the highly nonlinear neuro-musculo-skeletal mechanics of the limb, these collaterals could be a critical low-level enabler of learning, adaptation, and performance via higher-level brainstem, cerebellar and cortical mechanisms.

Significance

Muscles have velocity sensors controlled byγ-MNs that produce stretch reflexes which could disrupt voluntary limb movements. Whether and how severely those unmodulated stretch reflexes disrupt voluntary movement remains unclear, especially in realistic multi-articular limbs. Our neuromechanical simulations demonstrate that unmodulated stretch reflexes greatly disrupt movements. Modulating the stretch reflex by implementing an idealized version of a long-posited (but yet unclear)α-γco-activation greatly mitigates those perturbations. However, a collateral from theα-MN to theγ-MN (which has been reported among motoneurones but not interpreted in this way) achieves similar functionality. Our results suggest this modulation of the intensity of the stretch reflex by theα-MN collateral provides an effective mechanism to locally stabilize the disruptions from stretch reflexes.
Large Language Models for Detecting Body Weight Changes as Side Effects of Antidepressants in User-Generated Online Content
Authors: Yokoyama Taïoh , Natter Johan , Godet Julien
Published: December 2023

Objective

Healthcare websites allow patients to share their experiences with their treatments. Drug testimonials provide useful information for real-world evidence, particularly on the occurrence of side effects that may be underreported. We investigated the potential of large language models (LLMs) for detecting signals of body weight change as under-reported side effect of antidepressants in user-generated online content.

Materials and Methods

A database of 8,000 user-generated comments about the 32 FDA-approved antidepressants was collected from healthcare social websites. These comments were manually annotated under the supervision of drug experts. Several pre-trained LLMs derived from BERT were fine-tuned to automatically classify comments describing weight gain, weight loss, or the absence of reference to a weight change. Zero-shot classification was also performed. Performance was evaluated on a test set by measuring the weighted precision, recall, F1-score and the prediction accuracy.

Results

After fine-tuning, most of the BERT-derived LLMs showed weighted F1-scores above 97%. LLMs with higher number of parameters used in zero-shot classification almost reached the same performance. The main source of errors in predictions came from situations where the machine predicted falsely weight gain or loss, because the text mentioned these elements but for a different molecule than the one for which the comment was written.

Conclusion

Even fine-tuned LLMs with limited numbers of parameters showed interesting results for the detection of adverse events from online patient testimonials, suggesting they can be used at scale for real-world evidence.
Post-Transcriptional Methylation of Mitochondrial-tRNA Differentially Contributes to Mitochondrial Pathology
Authors: Maharjan Sunita , Gamper Howard , Yamaki Yuka , Henley Robert Y. , Li Nan-Sheng , Suzuki Takeo , Suzuki Tsutomu , Piccirilli Joseph A. , Wanunu Meni , Seifert Erin , Wallace Douglas C. , Hou Ya-Ming
Published: December 2023

Human mitochondrial tRNAs (mt-tRNAs), critical for mitochondrial biogenesis, are frequently associated with pathogenic mutations. These mt-tRNAs have unusual sequence motifs and require post-transcriptional modifications to stabilize their fragile structures. However, whether a modification that stabilizes a wild-type (WT) mt-tRNA structure would also stabilize its pathogenic variants is unknown. Here we show that theN1-methylation of guanosine at position 9 (m1G9) of mt-Leu(UAA), while stabilizing the WT tRNA, has an opposite and destabilizing effect on variants associated with MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes). This differential effect is further demonstrated by the observation that demethylation of m1G9, while damaging to the WT tRNA, is beneficial to the major pathogenic variant, improving its structure and activity. These results have new therapeutic implications, suggesting that theN1-methylation of mt-tRNAs at position 9 is a determinant of pathogenicity and that controlling the methylation level is an important modulator of mt-tRNA-associated diseases.
ST-GEARS: Advancing 3D Downstream Research through Accurate Spatial Information Recovery
Authors: Xia Tianyi , Hu Luni , Zuo Lulu , Zhang Yunjia , Xu Mengyang , Lu Qin , Zhang Lei , Cao Lei , Pan Taotao , Zhang Bohan , Ma Bowen , Chen Chuan , Guo Junfu , Shi Chang , Li Mei , Liu Chao , Li Yuxiang , Zhang Yong , Fang Shuangsang
Published: December 2023

Three-dimensional Spatial Transcriptomics has revolutionized our understanding of tissue regionalization, organogenesis, and development. However, to reconstruct single sections back to theirin situthree-dimensional morphology, existing approaches either only adopt gene expression information to guide reconstruction or overlook shape correction against experiment-induced section distortions. This leads to significant discrepancies between reconstruction results and the actualin vivolocations of cells, imposing unreliable spatial profiles to downstream analysis. To address these challenges, we propose ST-GEARS (Spatial Transcriptomics GEospatial profile recovery system through AnchoRS), which solves optimized ‘anchors’ betweenin situclosest spots utilizing expression and structural similarity across sections and recoversin vivospatial information under the guidance of anchors. By employing innovative Distributive Constraints into the Optimization scheme, it retrieves anchors with higher precision compared to existing methods. Taking these anchors as reference points, ST-GEARS first rigidly aligns sections, then introduces and infers Elastic Fields to counteract distortions. ST-GEARS denoises the fields using context information by Gaussian Denoising. Utilizing the denoised fields, it eliminates distortions and eventually recovers original spatial profile through innovative and mathematically proved Bi-sectional Fields Application. Studying ST-GEARS on both bi-sectional registration and complete tissue reconstruction across sectional distances and sequencing platforms, we observed its outstanding performance in spatial information recovery across tissue, cell, and gene levels compared to current approaches. Through this recovery, ST-GEARS provides precise and well-explainable ‘gears’ betweenin vivosituations and 3Din vitroanalysis, powerfully fueling the potential of biological discoveries.
Investigation of ice nucleation properties ofPseudomonas syringaebacterium and insoluble low molecular weight substances
Authors: Vorobeva D.E. , Majorina M.A. , Marchenko N.U. , Melnik B.S.
Published: December 2023

Control of the water freezing process is considerable in different fields of science and technology: from the artificial snow production to the cryopreservation of biological materials. To date, there is no conventional theory that predicts the influence of various biological and non-biological ice nucleators on the formation of ice and, accordingly, on the freezing point of supercooled water. In this work, we investigated the influence of bacteriumPseudomonas syringae, a biological ice nucleator, and heterodisperse insoluble powders of low molecular weight substances on the process of water freezing. AgCl, ZnO and SnO2were found to be ice nucleators. This property has not been described previously in the literature. It has also been established that insoluble low molecular weight substances affect both the freezing point of water and the temperature of coexistence of water and ice.
Maternal dietary deficiencies in folic acid or choline reduce primary neuron viability after exposure to hypoxia through increased levels of apoptosis
Authors: Yaldiko Alice , Coonrod Sarah , Marella Purvaja , Hurley Lauren , Jadavji Nafisa M.
Published: December 2023

Stoke is the leading cause of death and disability globally. By addressing modifiable risk factors, particularly nutrition, the prevalence of stroke and its dire consequences can be mitigated. One-carbon (1C) metabolism is a critical biosynthetic process that is involved in neural tube closure, neuronal plasticity, and cellular proliferation in the developing embryo. Folic acid and choline are two active components of 1C metabolism, we have previously demonstrated that maternal dietary deficiencies in folic acid or choline worsen stroke outcomes in offspring. However, there is insufficient data to understand the neuronal mechanisms involved. We exposed embryonic neurons of offspring, whom mothers were on folic acid or choline deficient diets, to hypoxia conditions for 6 hours and return to normoxic conditions for 24 hours to model an ischemic stroke and reperfusion injury. To determine whether increased levels of either folic acid or choline can rescue reduced neuronal viability, we supplemented cell media with folic acid and choline prior to and after exposure to hypoxia. Our results suggest that maternal dietary deficiencies in either folic acid or choline during pregnancy negatively impacts offspring neuronal viability after hypoxia. Furthermore, increasing levels of folic acid or choline prior to and after hypoxia have a beneficial impact on neuronal viability. The findings contribute to our understanding of the intricate interplay between maternal dietary factors, 1C metabolism, and the outcome of offspring to hypoxic events, emphasizing the potential for nutritional interventions in mitigating adverse outcomes.
Peribacillus frigoritoleransT7-IITJ, a potential biofertilizer, induces plant growth-promoting genes ofArabidopsis thaliana
Authors: Marik Debankona , Sharma Pinki , Chauhan Nar Singh , Jangir Neelam , Shekhawat Rajveer Singh , Verma Devanshu , Mukherjee Manasi , Abiala Moses , Roy Chandan , Yadav Pankaj , Sadhukhan Ayan
Published: December 2023

This study aimed to isolate plant growth and drought tolerance-promoting bacteria from the nutrient- poor rhizosphere soil of several plant species from the Thar desert and unravel their molecular mechanisms of plant growth promotion, to develop effective biofertilizers for arid agriculture. Among our isolates of Thar desert rhizobacteria,Enterobacter cloacaeC1P-IITJ,Kalamiella piersoniiJ4-IITJ, andPeribacillus frigoritoleransT7-IITJ, significantly enhanced root and shoot growth in the model plantArabidopsis thalianaunder PEG-induced drought stress in the lab. Whole genome sequencing and biochemical analyses of the non-pathogenic bacterium T7-IITJ revealed its plant growth-promoting traits, viz., solubilization of phosphate, iron, and nitrate and production of exopolysaccharides and auxin. Transcriptome analysis ofArabidopsis thalianainoculated with T7-IITJ and exposure to drought revealed the induction of plant genes for photosynthesis, auxin and jasmonate signaling, nutrient mining and sequestration, redox homeostasis, and secondary metabolite biosynthesis pathways related to beneficial bacteria-plant interaction, but repression of many stress-responsive genes. Biochemical analyses indicated enhanced proline, chlorophyll, iron, phosphorous, and nitrogen content and reduced reactive oxygen species in plant tissues due to T7-IITJ inoculation. This bacterium could also improve the germination and seedling growth ofTephrosia purpurea,Triticum aestivum,andSetaria italicaunder drought. Additionally, T7-IITJ inhibited the growth of two plant pathogenic fungi,Rhizoctonia solani,andFusarium oxysporum. These results suggestP. frigoritoleransT7-IITJ is a potent biofertilizer which can regulate plant genes promoting growth and drought tolerance.
Discovery of anthelmintic small molecules in the Medicines for Malaria Venture’s COVID and Global Health Priority Boxes using an infrared-based assay forCaenorhabditis elegansmotility
Authors: Sun Yujie Uli , Liu Lawrence J. , Caffrey Conor R.
Published: December 2023

Background

Parasitic nematodes are a public health problem globally, and an economic burden on animal and plant agricultural industries. With their ability to generate drug resistance, new anthelmintic compounds must be constantly sourced.

Methods

Using the free-living nematode,Caenorhabditis elegans,in an infrared-based motility assay, we screened 400 compounds from two open-source, small-molecule collections distributed by the Medicines for Malaria Venture, namely, the COVID Box and Global Health Priority Box. The screening assay was first validated for worm number, DMSO concentration and final volume.

Results

Primary and secondary (time- and concentration-dependent) screens of both boxes, identified twelve compounds as hits; nine of which were known anthelmintics. Three novel anthelmintic hits, flufenerim, flucofuron and indomethacin were identified with EC50values ranging from 0.211 to 23.174 µM. Counter toxicity screens with HEK293 cells indicated varying degrees of toxicity with EC50values ranging from 0.453 to >100 µM.

Conclusions

AC. elegansmotility assay was optimized and used to screen two recently-released, small molecule libraries. One or more of these three novel active compounds might serve as starting points for the development of new anthelmintics.
Toward Best Practice in Identifying Subtle Differential Expression with RNA-seq: A Real-World Multi-Center Benchmarking Study Using Quartet and MAQC Reference Materials
Authors: Wang Duo , Liu Yaqing , Zhang Yuanfeng , Chen Qingwang , Han Yanxi , Hou Wanwan , Liu Cong , Yu Yin , Li Ziyang , Li Ziqiang , Zhao Jiaxin , Zheng Yuanting , Shi Leming , Li Jinming , Zhang Rui
Published: December 2023

Translating RNA-seq into clinical diagnostics requires ensuring the reliability of detecting clinically relevant subtle differential expressions, such as those between different disease subtypes or stages. Moreover, cross-laboratory reproducibility and consistency under diverse experimental and bioinformatics workflows urgently need to be addressed. As part of the Quartet project, we presented a comprehensive RNA-seq benchmarking study utilizing Quartet and MAQC RNA reference samples spiked with ERCC controls in 45 independent laboratories, each employing their in-house RNA-seq workflows. We assessed the data quality, accuracy and reproducibility of gene expression and differential gene expression and compared over 40 experimental processes and 140 combined differential analysis pipelines based on multiple ‘ground truths’. Here we show that real-world RNA-seq exhibited greater inter-laboratory variations when detecting subtle differential expressions between Quartet samples. Experimental factors including mRNA enrichment methods and strandedness, and each bioinformatics step, particularly normalization, emerged as primary sources of variations in gene expression and have a more pronounced impact on the subtle differential expression measurement. We underscored the pivotal role of experimental execution over the choice of experimental protocols, the importance of strategies for filtering low-expression genes, and optimal gene annotation and analysis tools. In summary, this study provided best practice recommendations for the development, optimization, and quality control of RNA-seq for clinical diagnostic purposes.
Isotope geolocation and population genomics inVanessa cardui:Short- and long-distance migrants are genetically undifferentiated
Authors: Reich Megan S. , Shipilina Daria , Talla Venkat , Bahleman Farid , Kébé Khadim , Berger Johanna L. , Backström Niclas , Talavera Gerard , Bataille Clément P.
Published: December 2023

The painted lady butterflyVanessa carduiis renowned for its virtually cosmopolitan distribution and the remarkable long-distance migrations that are part of its annual, multi-generational migratory cycle. Recently,V. carduiindividuals were found north and south of the Sahara in the autumn, suggesting distinct migratory behaviours within the species. However, the evolutionary and ecological factors shaping these differences in migratory behaviour remain largely unexplored. Here, we performed whole-genome resequencing and analysed the hydrogen and strontium isotopes of 40V. carduiindividuals simultaneously collected in the autumn from regions both north and south of the Sahara. Our investigation revealed two main migratory groups: (i) short-distance migrants, journeying from temperate Europe to the circum-Mediterranean region and (ii) long-distance migrants, originating from Europe, crossing the Mediterranean Sea and Sahara, and reaching West Africa, covering up to over 4,000 km. Despite these stark differences in migration distance, a genome-wide analysis revealed that both short- and long-distance migrants belong to a single intercontinental panmictic population extending from northern Europe to sub-Saharan Africa. Contrary to common biogeographic patterns, the Sahara is not a catalyst for population structuring in this species. No significant genetic differentiation or signs of adaptation and selection were observed between the two migratory phenotypes (pairwise FST= 0.001 ± 0.006). Nonetheless, two individuals, which were early arrivals to West Africa and covered longer migration distances, exhibited some genetic differentiation. The lack of genetic structure between short- and long-distance migrants suggests that migration distance inV. carduiis a plastic response to environmental conditions.

Significance statement

Although migratory insects dominate living biomass fluxes and impact agriculture, ecosystems, and human communities, little is known about the controls of their migratory behavior. Our study develops an interdisciplinary framework, applied to the migratory butterflyV.cardui, to explore the genetic basis of variation in insect migration behavior. We leverage new generation isotope geolocation techniques to uncover striking differences in butterfly behaviour, with some individuals migrating short distances within the circum-Mediterranean region and others migrating thousands of kilometers across the Mediterranean Sea and Sahara. This major difference does not coincide with genetic differentiation or population structure and is likely a plastic response to environmental cues. This study provides a ground-breaking framework to study migration in insects.
Switching circuits: Modulating NK cell response to TGF-β using novel receptors
Authors: Turk Rebekah , Guo Lan , Belmont Brian J. , Bogard Nick , Chen Aye T. , Williams Maddie D. , Young Mary , Stone Matthew R. , Daines Bryce , Darnell Max
Published: December 2023

Engineered natural killer (NK) cells offer a promising treatment strategy for multiple therapeutic areas, yet tuning cell function to diverse environmental and inhibitory contexts remains a significant challenge. An attractive strategy for functional rescue in the presence of inhibitory ligands is the use of switch receptors, surface-expressed chimeric receptors that convert an external inhibitory cue into an intracellular activation signal. Here, we discover novel engineered switch receptors in NK cells that are responsive to TGF-β, a soluble inhibitory factor present in many therapeutic contexts. Through a pooled screen of an 11,131 member library, we identified multiple novel signaling endodomains and endodomain combinations that improve both the acute cytotoxicity and persistence of NK cells in the presence of TGF-β, demonstrating a novel and flexible approach to switch receptor discovery.
RPL22 is a tumor suppressor in MSI-high cancers and a key splicing regulator of MDM4
Authors: Weinstein Hannah N.W. , Hu Kevin , Fish Lisa , Chen Yih-An , Allegakoen Paul , Hui Keliana S. F. , Pham Julia H. , Baco Maria B. , Song Hanbing , Giacomelli Andrew O. , Vazquez Francisca , Ghandi Mahmoud , Goodarzi Hani , Huang Franklin W.
Published: December 2023

Microsatellite instability high (MSI-H) tumors are malignant tumors that, despite harboring a high mutational burden, often have intactTP53. One of the most frequent mutations in MSI-H tumors is a frameshift mutation inRPL22, a ribosomal protein. Here, we identifiedRPL22as a modulator ofMDM4splicing through an alternative splicing switch in exon 6.RPL22loss increasesMDM4exon 6 inclusion, cell proliferation, and augments resistance to the MDM inhibitor Nutlin-3a. RPL22 represses expression of its paralog, RPL22L1, by mediating the splicing of a cryptic exon corresponding to a truncated transcript. Therefore, damaging mutations in RPL22 drive oncogenic MDM4 induction and reveal a common splicing circuit in MSI-H tumors that may inform therapeutic targeting of the MDM4-p53 axis and oncogenic RPL22L1 induction.
Morphological signatures of neurogenesis and neuronal migration in hypothalamic vasopressinergic magnocellular nuclei of the adult rat
Authors: Zhang Limei , Zetter Mario A. , Hernández Vito S. , Hernández-Pérez Oscar R. , Jáuregui-Huerta Fernando , Krabichler Quirin , Grinevich Valery
Published: December 2023

Arginine vasopressin (AVP)-magnocellular neurosecretory system (AVPMNS) in the hypothalamus plays a critical role in homeostatic regulation as well as in allostatic motivational behaviors. However, it remains unclear whether adult neurogenesis exists in the AVPMNS. By using immunoreaction against AVP, neurophysin II, glial fibrillar acidic protein (GFAP), cell division marker (Ki67), migrating neuroblast markers (doublecortin, DCX), microglial marker Iba1, and 5′-bromo-2′-deoxyuridine (BrdU), we report morphological evidence that low rate neurogenesis and migration occur in adult AVPMNS in rat hypothalamus. Tangential AVP/GFAP migration routes and AVP/DCX neuronal chains as well as ascending AVP axonal scaffolds were observed. Chronic water deprivation significantly increased the BrdU+ nuclei within both the SON and PVN. These findings raise new questions about AVPMNS’s potential hormonal role for brain physiological adaptation across the lifespan, with possible involvement in coping with homeostatic adversities.
Injectable 3D microcultures enable intracerebral transplantation of mature neurons directly reprogrammed from patient fibroblasts
Authors: Kajtez Janko , Nilsson Fredrik , Laurin Kerstin , Bruzelius Andreas , Cepeda-Prado Efrain , Birtele Marcella , Barker Roger A. , Herborg Freja , Ottosson Daniella Rylander , Storm Petter , Fiorenzano Alessandro , Habekost Mette , Parmar Malin
Published: December 2023

Direct reprogramming of somatic cells into induced neurons (iNs) has become an attractive strategy for the generation of patient-specific neurons for disease modeling and regenerative neuroscience. To this end, adult human dermal fibroblasts (hDFs) present one of the most relevant cell sources. However, iNs generated from adult hDFs using two-dimensional (2D) cultures poorly survive transplantation into the adult brain in part due to the need for enzymatic or mechanical cellular dissociation before transplantation. Three-dimensional (3D) culturing methodologies have the potential to overcome these issues but have largely been unexplored for the purposes of direct neuronal reprogramming. Here we report a strategy for directin vitroreprogramming of adult hDFs inside suspension 3D microculture arrays into induced DA neurospheroids (iDANoids). We show that iDANoids express neuronal and DA markers and are capable of firing mature action potentials and releasing dopamine. Importantly, they can be gently harvested and transplanted into the brain of a Parkinson’s disease rat model to reproducibly generate functionally integrated neuron-rich grafts. The 3D culturing approach presented here thus eliminates a major bottleneck in direct neuronal reprogramming field and, due to its simplicity and versatility, could readily be adapted as a culturing platform used for a broad range of transplantation studies as well as disease modeling.
Integrated omics analysis unveils a DNA damage response to neurogenic injury
Authors: Hashemi Gheinani Ali , Sack Bryan S. , Bigger-Allen Alex , Thaker Hatim , Atta Hussein , Lambrinos George , Costa Kyle , Doyle Claire , Gharaee-Kermani Mehrnaz , Patalano Susan , Piper Mary , Cotellessa Justin F. , Vitko Dijana , Li Haiying , Kadayil Prabhakaran Manubhai , Cristofaro Vivian , Froehlich John , Lee Richard S. , Yang Wei , Sullivan Maryrose P. , Macoska Jill A. , Adam Rosalyn M.
Published: December 2023

Spinal cord injury (SCI) evokes profound bladder dysfunction. Current treatments are limited by a lack of molecular data to inform novel therapeutic avenues. Previously, we showed systemic inosine treatment improved bladder function following SCI in rats. Here, we applied multi-omics analysis to explore molecular alterations in the bladder and their sensitivity to inosine following SCI. Canonical pathways regulated by SCI included those associated with protein synthesis, neuroplasticity, wound healing, and neurotransmitter degradation. Upstream regulator analysis identified MYC as a key regulator, whereas causal network analysis predicted multiple regulators of DNA damage response signaling following injury, including PARP-1. Staining for both DNA damage (γH2AX) and PARP activity (poly-ADP-ribose) markers in the bladder was increased following SCI, and attenuated in inosine-treated tissues. Proteomics analysis suggested that SCI induced changes in protein synthesis-, neuroplasticity-, and oxidative stress-associated pathways, a subset of which were shown in transcriptomics data to be inosine-sensitive. These findings provide novel insights into the molecular landscape of the bladder following SCI, and highlight a potential role for PARP inhibition to treat neurogenic bladder dysfunction.

Synopsis

Employed a multi-omics approach, integrating both transcriptomic and proteomic analyses, to investigate the molecular response in a rat model of spinal cord injury (SCI) and the therapeutic effect of inosine.

Discovered multiple regulators of the DNA damage response, including PARP-1, using causal network analysis.

Observed decreased markers of DNA damage and PARP activity in inosine-treated tissues, indicating the therapeutic potential of inosine in neurogenic dysfunction.

Identified significant alterations in molecular pathways associated with protein synthesis, neuroplasticity, wound healing, and neurotransmitter degradation after SCI, and their modulation by inosine, highlighting its neuroprotective effects beyond DNA damage repair.
Several theoretical issues on the socialist utilization of capital
Authors: Qiu Haiping
Published: December 2023

Purpose

In the new development stage of comprehensively building a socialist modern state, it is imperative to adhere to the guidance of Xi Jinping Thought on Socialism with Chinese Characteristics for a New Era, comprehensively summarize China's practical experiences in economic development, strengthen research on capital issues, construct theories of socialist political economy with Chinese characteristics regarding capital and provide scientific theoretical guidance for further promoting the positive role of various types of capital while preventing and overcoming their negative effects, which is a major theoretical issue and a glorious task for the theoretical and economic circles in China.

Design/methodology/approach

From the perspective of Marx's theory on capital and historical development, modern capital represents the organizational mode of socialized mass production and market economy. It serves as both the economic foundation of bourgeois society and a tool for socialist economic development.

Findings

The market economy represents an inevitable historical stage and form of socialist economic development, necessitating the adoption of capital as an organizational form within socialist economies.

Originality/value

The utilization of capital to advance a socialist economy is a remarkable achievement by the CPC and Chinese people, representing a significant innovation in both theory and practice. The role of capital is inherently dual under any social condition. In the context of a socialist system, capital can play a positive role effectively, and its behavior can be guided and regulated correctly to curb its negative or even destructive impact.
Transfer of farmland operation rights and improvement of productivity of farmers: theory and empirical evidence
Authors: Mao Peihua , Xu Ji , He Xiaodan , Zhou Yahong
Published: December 2023

Purpose

The results of this study have significant policy implications for charting a new course toward enhancing agricultural productivity among Chinese farmers.

Design/methodology/approach

By establishing a rural household decision-making model based on the transfer market of farmland operation rights, this paper systematically analyzes the effects of land transfer-in and land transfer-out on the productivity (per labor income) of rural households. The authors conducted basic regression analysis and robustness tests using propensity score-matching and proxy variable approaches based on the micro survey data from rural households in 30 counties in 21 provinces/municipalities/autonomous regions in 2013.

Findings

After the completion of land transfer, the total productivity of rural households transferring in lands will increase with an increase in the agricultural productivity; the total productivity of rural households transferring out land will increase due to a rise in non-agricultural productivity and the absolute total productivity of rural households not involved in land transfer will remain unchanged.

Originality/value

Unlike previous literature, this paper discusses the impacts of land transfer-in and transfer-out on total productivity, agricultural productivity and non-agricultural productivity among various rural households (i.e. those transferring in land, transferring out land or which are self-sufficient).
How does age and gender of the employees influence human resource practices–employee competencies relationship?
Authors: Kaur Sukhpreet
Published: December 2023

Purpose

Applying resource-based view and the configurational approach theory, this study seeks to understand the moderating role of age and gender between human resource practices and employee competencies relationship.

Design/methodology/approach

43 food processing firms of India participated in the study. Applying multilevel approach, the responses of 295 human resource managers and 3,557 employees were used for the analysis.

Findings

The human resource practices–employee competencies relationship was stronger in the case of young employees. Furthermore, the relationship was better in case of male employees over female employees. The results urge for greater attention toward age and gender diversity issues while tailoring human resource practices for enhancing employee skills. This article contributes the human resource management literature by exploring the role of age and gender, which has been used as the control variables as the moderating variables for governing the human resource practices–employee competencies relationship.

Practical implications

Special focus can be placed on extensive custom in-house training and development activities. Proper division of work can be done for new employees and experienced employees depending upon their learning capabilities. The firms can do so by either implementing formal or informal organizational structures to achieve full gains. Firms should focus largely on narrowing the development practices adopted for diverse age groups of workforce population. The four practices proposed by the Organization for Economic Cooperation and Development (2006) for ensuring effectiveness of development practices and its impact on old age employee effectiveness and attitude should be put in practice.

Originality/value

The originality of this study lies in its exploration of the intricate interplay among age, gender and human resource practices in shaping employee competencies. By understanding how these factors interact within the human resource practices–employee competencies framework, this research offers a unique perspective on the evolving workforce dynamics. It goes beyond the conventional human resource management strategies to uncover nuanced insights, shedding light on tailored approaches that consider the specific needs and aspirations of diverse employees. This innovative perspective contributes to a more inclusive, efficient and adaptable work environment, enriching both the academic understanding of human resources and the practical implementation of strategies for contemporary organizations.
Curating the elegance of Chikankari: a case of Ada
Authors: Dwivedi Hemverna , Kumar Shubham
Published: December 2023

Learning outcomes

Upon completion of the case study, the students will be able to conceptualize the importance of brand differentiation; suggest the implications of brand differentiation in the context of the traditional Chikan art form; examine the aspect of a brand’s product portfolio management; and critically analyse the competitive advantages of the brand using the VRIO framework.

Case overview/synopsis

The Chikankari art form gained worldwide recognition. In fact, it also received a geographical indication (GI) tag which is important for international branding. The case is centred around an entrepreneur, Mr. Vinod Punjabi, who redefined the essence of the existing Chikan art form by value addition in terms of intricate designs, patterns and exclusivity. He founded the brand Ada in 2015 aimed at preserving the traditional art form while curating elegance and exclusivity in its product portfolio. The case outlined Punjabi’s journey. The protagonist carefully analysed the open and unorganized Chikankari market and adopted the strategy of brand differentiation to stand apart from the competitors. Punjabi’s daughter, the chief operations officer of Ada, described the aspects. The journey was arduous, but over the years, Ada emerged as a successful name in the Chikankari market. The brand’s intent of becoming synonymous with Chikankari was successful owing to its authentic and exclusive hand-crafted products in the competitive environment of machine-made replicas. Furthermore, the brand also consistently worked on the aesthetic appearance of its store to attract a wide range of customers. Punjabi ensured that the brand was an amalgamation of all the essential elements for its survival in the long run.

Complexity academic level

The case is aimed for students pursuing bachelor’s and master’s degrees in business administration/diploma in management, marketing and entrepreneurship. Furthermore, it will assist the management trainees in gaining valuable insights.

Supplementary materials

Teaching notes are available for educators only.

Subject code

CSS 8: Marketing.