bluuebunny/crossref_metadata_2025 huggingface dataset:
Hereditary coagulation factor XI deficiency: a rare or neglected disease? Results from a retrospective, single-centre cohort in northern Italy
Authors: Canovi Simone , Leone Maria Cristina , Depietri Luca , Veropalumbo Maria Rosaria , Pilia Annalisa , Granito Maria , Bonanno Antonio , Casali Annamaria , Colla Rossana , Ghirarduzzi Angelo
Published: December 2023

To examine real-life clinical data regarding hereditary factor XI (FXI) deficiency from a secondary care centre. Retrospective review of clinical records for every FXI:C 0.7 IU/ml or less reported from 2012 to 2020. Seventy-nine patients were included. Six (7.6%) had a severe deficiency (FXI:C <0.2 IU/ml). Only 55 (69.6%) patients were referred to the Haemostasis Centre. Among them, six (15%) were subsequently not identified at increased haemorrhagic risk before a surgical/obstetrical procedure. Thirty-three (41.8%) experienced at least one bleeding event, minor (25 patients) and/or major (16 patients). Minor bleedings were predominantly spontaneous and more frequent in women, major events were mainly provoked. No correlation was found between FXI:C and risk of bleeding (P = 0.9153). Lower FXI:C, but not a positive bleeding history, was related with higher likelihood of being referred to the Haemostasis Centre (P = 0.0333). Hereditary FXI deficiency prevalence is likely underestimated, real-life clinical practices outside reference centres could be suboptimal.
Nurse Leader Attitudes and Beliefs Regarding Medical Errors
Authors: Prothero Marie M. , Huefner Katherine , Sorhus Madeline
Published: December 2023

OBJECTIVE

This study aimed to explore nurse leader attitudes and beliefs about medical errors.

BACKGROUND

The perfectibility model suggests errors are avoidable if nurses are trained and follow safety guidelines. This impacts how nurse leaders approach medical errors. Nurse leaders (NLs) may be the first person to whom a nurse reports an error. Leaders support nurses through the investigation process and subsequent recovery.

METHODS

A cross-sectional quantitative study was conducted to determine NL attitudes toward medical errors using the Medical Error Attitude Scale (MEAS).

RESULTS

MEAS scores were high in all categories. Medical error perception was significant for NLs with institutional support programs and when compared with job titles. Medical error approach and perception were significant for NLs with direct reports who had committed a medical error.

CONCLUSION

This study provides insight into NLs' views on medical errors, awareness of NLs who have had nurses involved in medical errors, and formal caregiver support programs.
18F-FDG PET/CT in Renal Allograft Tuberculosis Mimicking as Posttransplant Malignancy
Authors: Moideen Amal , Singh Harmandeep , Kumar Rajender , Naik Sachin Motiram , Gupta Anna , Sekar Aravind , Nada Ritambhra
Published: December 2023

The most common complications after the renal transplant are infections and malignancies, including posttransplant lymphoproliferative disorders. Tubercular infection in renal allograft recipients is a relatively rare entity. However, nonspecific constitutional symptoms often delay diagnosis, leading to significant morbidity and mortality. We present the 18F-FDG PET/CT findings in a patient with renal allograft tuberculosis who had clinical and imaging suspicion of posttransplant lymphoproliferative disorder or renal cell carcinoma. Histopathology from the renal lesion revealed tuberculosis.
Incidental Detection of Urinary Leakage on FDG PET/CT Imaging
Authors: Hou Naifeng , Fan Chengzhong , Shen Guohua
Published: December 2023

A 57-year-old woman previously diagnosed as cervical cancer underwent an 18F-FDG PET/CT scan for restaging. A pelvic encapsulated effusion with intense FDG accumulation was incidentally revealed. The tracer activity was similar to that of urine, indicating presence of urinary leakage. Subsequent CT urography confirmed the complete avulsion of the right distal ureter.
Combined Liver Transplant and Cardiac Surgery
Authors: Wehrle Chase J , Schlegel Andrea , Khalil Mazhar , Rotroff Daniel , Del Prete Luca , Maspero Marianna , Raj Roma , Frankel William C , Eghtesad Bijan , Aucejo Federico , Fujiki Masato , Kwon Choon David , Kim Jaekeun , Tong Michael Z Y , Unai Shinya , Cywinski Jacek , Modaresi Esfeh Jamak , Fares Maan , Pita Alejandro , Miller Charles , Quintini Cristiano , Hashimoto Koji , Diago-Uso Teresa
Published: December 2023

Objective:

We aim to report our institutional outcomes of single-staged combined liver transplantation (LT) and cardiac surgery (CS).

Summary Background Data:

Concurrent LT and CS is a potential treatment for combined cardiac dysfunction and end-stage liver disease, yet only 54 cases have been previously reported in the literature. Thus, the outcomes of this approach are relatively unknown, and this approach has been previously regarded as extremely risky.

Methods:

Thirty-one patients at our institution underwent combined cardiac surgery and liver transplant. Patients with at least one-year follow-up were included. The Leave-One-Out Cross-Validation (LOOCV) machine-learning approach was used to generate a model for mortality.

Results:

Median follow-up was 8.2 years (IQR 4.6-13.6 y). One- and five-year survival was 74.2% (N=23) and 55% (N=17), respectively. Negative predictive factors of survival included recipient age>60 years (P=0.036), NASH-cirrhosis (P=0.031), Coronary Artery Bypass-Graft (CABG)-based CS (P=0.046) and pre-operative renal dysfunction (P=0.024). The final model demonstrated that renal dysfunction had a relative weighted impact of 3.2 versus CABG (1.7), age ≥60y (1.7) or NASH (1.3). Elevated LT+CS risk score was associated with an increased five-year mortality after surgery (AUC=0.731, P=<0.001). Conversely, the widely accepted STS-PROM calculator was unable to successfully stratify patients according to 1- (P>0.99) or 5-year (P=0.695) survival rates.

Conclusions:

This is the largest series describing combined LT+CS, with joint surgical management appearing feasible in highly selected patients. CABG and pre-operative renal dysfunction are important negative predictors of mortality. The four-variable LT+CS score may help predict patients at high risk for post-operative mortality.
Evaluating Clinical Presentation and Long-Term Outcomes in Individuals with Genetic and Non-Genetic Epilepsy Treated with Epilepsy Surgery: A Single-Center Study
Authors: Ivaniuk Alina , Boßelmann Christian M , Pestana-Knight Elia , Zhang Xiaoming , Jehi Lara , Bingaman William , Najm Imad , Lal Dennis
Published: December 2023

Background

Many genetic epilepsy disorders are characterized by focal epilepsy or exhibit focal or lateralized features, which make individuals with such conditions potential surgical candidates. However, surgical outcomes in epilepsy caused by germline genetic variants and value of genetic testing in presurgical assessment remains unclear.

Methods

This retrospective cross-sectional study included people with germline genetic epilepsy and non-genetic epilepsy identified among 2879 people with epilepsy who underwent resective surgery or laser ablation at Cleveland Clinic in years 1997-2022. We separated individuals with germline genetic epilepsies into mTORopathies (clinically or genetically diagnosed tuberous sclerosis and genetically diagnosed GATOR-related epilepsies) and other genetic etiologies. We compared clinical variables between the groups using Kruskal-Wallis and Fisher tests as appropriate. We analyzed cumulative seizure recurrence risk over 5 years with Kaplan-Meier curves and used Cox proportional hazards model for univariate and multivariate analysis. We repeated the analysis after matching both genetic sub-groups to non-genetic group 1:1 by propensity scores estimated by a generalized linear model.

Results

We included 49 individuals with genetic epilepsies (32 individuals with mTORopathies and 17 individuals with other genetic etiologies) and 585 individuals with non-genetic epilepsy. Individuals with genetic epilepsies in both groups were younger at seizure onset (p<0.001) and at surgery (p<0.001), had a higher preoperative seizure frequency (p<0.001), higher rate of developmental delay (p<0.001), lower rate of focal interictal (p=0.005) and ictal (p<0.001) findings on EEG, and more extratemporal and extensive resections (p<0.001). At the last follow-up, individuals with other genetic etiologies had a lower rate of seizure freedom than individuals with mTORopathies and non-genetic etiologies; still, 70.6% achieved seizure reduction. Individuals with other genetic etiologies had a higher cumulative risk of seizure recurrence at 5 years both in univariate (HR 3.07, 95% CI 1.4-6.74) and multivariate (HR 3.81, 95% CI 1.69-8.62, p=0.001) analyses, which was reproducible in a matched cohort analysis.

Conclusions

People with germline genetic epilepsy across multiple etiologies could be surgical candidates. However, seizure recurrence may be faster in genetic epilepsies other than mTORopathies. Further studies are required to clarify surgical candidacy in different genetic epilepsy disorders and establish value of presurgical genetic testing.
Chloroplast genome-based genetic resources for Japan’s threatened subalpine forests via genome skimming
Authors: Worth James R.P. , Kikuchi Satoshi , Kanetani Seiichi , Takahashi Daiki , Aizawa Mineaki , Marchuk Elena A. , Choi Hyeok Jae , Polezhaeva Maria A. , Sheiko Viktor V. , Ueno Saneyoshi
Published: December 2023

The Japanese subalpine zone is dominated by a distinct and ecologically important conifer rich forest biome, subalpine coniferous forests, that are an outlier of the extensive boreal forests of Eurasia. While being relatively intact compared to other forest biomes in Japan, subalpine coniferous forests are under significant threat from deer browsing, global warming and small populations size effects. However, there is a severe lack of genetic resources available for the study of this biome’s major constituent plant species. This study aims to develop chloroplast genome-based genetic resources for 12 widespread subalpine tree and shrub species via genome skimming of whole genomic DNA using short reads (100-150 bp in length). For 10 species, whole chloroplast genomes were assembled viade novo-based methods from 4-10 individuals per species sampled from across their ranges in Japan and, for non-Japanese endemic species, elsewhere in northeast Asia. A total of 566 single nucleotide polymorphisms for Japanese samples and 768 for all samples (varying from 2 to 202 per species) were identified which were distributed in geographically restricted lineages in most species. In addition, between 9 to 58 polymorphic simple sequence repeat regions were identified per species. For two Ericaceae species (Rhododendron brachycarpumandVaccinium vitis-idaea) characterized by large chloroplast genomes,de novoassembly failed, but single nucleotide polymorphisms could be identified using reference mapping. This data will be useful for genetic studies of the taxonomic relationship of populations within Japan and to other parts of northeast Asia, investigating phylogeographic patterns within species, conservation genetics and has potential application for studies of environmental and ancient DNA.
Yeast9: A Consensus Yeast Metabolic Model Enables Quantitative Analysis of Cellular Metabolism By Incorporating Big Data
Authors: Zhang Chengyu , Sánchez Benjamín J. , Li Feiran , Eiden Cheng Wei Quan , Scott William T. , Liebal Ulf W. , Blank Lars M. , Mengers Hendrik G. , Anton Mihail , Rangel Albert Tafur , Mendoza Sebastián N. , Zhang Lixin , Nielsen Jens , Lu Hongzhong , Kerkhoven Eduard J.
Published: December 2023

Genome-scale metabolic models (GEMs) can facilitate metabolism-focused multi-omics integrative analysis. Since Yeast8, the yeast-GEM ofSaccharomyces cerevisiae, published in 2019, has been continuously updated by the community. This have increased the quality and scope of this model, culminating now in Yeast9. To evaluate its predictive performance, we generated 163 condition-specific GEMs constrained by single-cell transcriptomics from osmotic pressure or normal conditions. Comparative flux analysis showed that yeast adapting to high osmotic pressure benefits from upregulating fluxes through the central carbon metabolism. Furthermore, combining Yeast9 with proteomics revealed metabolic rewiring underlying its preference in nitrogen sources. Lastly, we created strain-specific GEMs (ssGEMs) constrained by transcriptomics for 1229 mutant strains. Well able to predict the strains’ growth rates, fluxomics from those large-scale ssGEMs outperformed transcriptomics in predicting functional categories for all studied genes in machine-learning models. Based on those findings we anticipate that Yeast9 will empower systems biology studies of yeast metabolism.
Synthetic Lethality Screening with Recursive Feature Machines
Authors: Cai Cathy , Radhakrishnan Adityanarayanan , Uhler Caroline
Published: December 2023

Synthetic lethality refers to a genetic interaction where the simultaneous perturbation of gene pairs leads to cell death. Synthetically lethal gene pairs (SL pairs) provide a potential avenue for selectively targeting cancer cells based on genetic vulnerabilities. The rise of large-scale gene perturbation screens such as the Cancer Dependency Map (DepMap) offers the opportunity to identify SL pairs automatically using machine learning. We build on a recently developed class of feature learning kernel machines known as Recursive Feature Machines (RFMs) to develop a pipeline for identifying SL pairs based on CRISPR viability data from DepMap. In particular, we first train RFMs to predict viability scores for a given CRISPR gene knockout from cell line embeddings consisting of gene expression and mutation features. After training, RFMs use a statistical operator known as average gradient outer product to provide weights for each feature indicating the importance of each feature in predicting cellular viability. We subsequently apply correlation-based filters to re-weight RFM feature importances and identify those features that are most indicative of low cellular viability. Our resulting pipeline is computationally efficient, taking under 3 minutes for analyzing all 17, 453 knockouts from DepMap for candidate SL pairs. We show that our pipeline more accurately recovers experimentally verified SL pairs than prior approaches. Moreover, our pipeline finds new candidate SL pairs, thereby opening novel avenues for identifying genetic vulnerabilities in cancer.
The dual coding of a single sex pheromone receptor in regulating the mating behavior of Asian HoneybeeApis cerana
Authors: Ke Haoqin , Bohbot Jonathan D. , Chi Yongjuan , Duan Shiwen , Ma Xiaomei , Ren Bingzhong , Wang Yinliang
Published: December 2023

In honeybee society, a virgin queen usually mates only once with several drones before founding a colony. For the rest of her prolific life, she will not engage in subsequent mating events. In the Asian honeybeeApis cerana, the mechanisms controlling this reproductive strategy involves the queen-released mandibular pheromone (QMP). This pheromone blend regulates the physiology and reproductive behavior of workers and drones. Its main component, 9-oxo-(E)-2-decenoic acid (9-ODA), acts as a sex pheromone and attracts drones. However, how the QMP prevents additional mating later in the queen’s life remains elusive. Using behavioral and chemical analysis, we show that the QMP component methylp-hydroxybenzoate (HOB) released by mated queens inhibits male attraction to 9-ODA. Furthermore,in vivoelectroantennogram and single sensillum recording data indicated that HOB alone significantly reduces the spontaneous spike activity of 9-ODA-sensitive olfactory receptor neurons (ORNs). To explore the molecular mechanism underlying this inverse effect, we conducted qPCR and in situ hybridization assays. The results indicated thatAcerOr11is specifically expressed in sensilla placodea from the drone’s antennae, which are the sensilla that narrowly respond to both 9-ODA and HOB. We then cloned and expressedAcerOr11in a Xenopus oocyte expression system, whereAcerOr11induced robust inward (regular) currents in response to 9-ODA. Intriguingly, HOB induced inverse currents in a dose-dependent manner. This suggests that HOB may act as an inverse agonist againstAcerOr11, providing additional odor-coding information. Based on these findings, we propose a model in whichAcerOr11function as a dual modulators in regulating the mating behavior ofA. cerana. The inverse agonist, HOB, can help manage the population dynamics of honeybees in apiculture.
Adjuvant nivolumab, capecitabine or the combination in patients with residual triple-negative breast cancer: the OXEL randomized phase II study
Authors: Lynce Filipa , Mainor Candace , Donahue Renee N. , Geng Xue , Jones Greg , Schlam Ilana , Wang Hongkun , Toney Nicole J. , Jochems Caroline , Schlom Jeffrey , Zeck Jay , Gallagher Christopher , Nanda Rita , Graham Deena , Stringer-Reasor Erica M , Denduluri Neelima , Collins Julie , Chitalia Ami , Tiwari Shruti , Nunes Raquel , Kaltman Rebecca , Khoury Katia , Gatti-Mays Margaret , Tarantino Paolo , Tolaney Sara M. , Swain Sandra M , Pohlmann Paula , Parsons Heather A. , Isaacs Claudine
Published: December 2023

Chemotherapy and immune checkpoint inhibitors have a role in the post-neoadjuvant setting in patients with triple-negative breast cancer (TNBC). However, the effects of nivolumab, a checkpoint inhibitor, capecitabine, or the combination in changing peripheral immunoscore (PIS) remains unclear. This open-label randomized phase II OXEL study (NCT03487666) aimed to assess the immunologic effects of nivolumab, capecitabine, or the combination in terms of the change in PIS (primary endpoint). Secondary endpoints include the presence of ctDNA, toxicity, clinical outcomes at 2-years and association of ctDNA and PIS with clinical outcomes. Forty-five women with TNBC and residual invasive disease after standard neoadjuvant chemotherapy were randomized to nivolumab, capecitabine, or the combination. Here we show that a combination of nivolumab plus capecitabine leads to a greater increase in PIS from baseline to week 6 (91%) compared with nivolumab (47%) or capecitabine (53%) alone (log-rank p = 0.08), meeting the pre-specified primary endpoint. In addition, the presence of circulating tumor DNA (ctDNA) was associated with disease recurrence, with no new safety signals in the combination arm. Our results provide efficacy and safety data on this combination in TNBC and support further development of PIS and ctDNA analyses to identify patients at high risk of recurrence.
Performance of ICD-10-based injury severity scores in pediatric trauma patients using the ICD-AIS map and survival rate ratios
Authors: Hojeij Rayan , Brensing Pia , Nonnemacher Michael , Kowall Bernd , Felderhoff-Müser Ursula , Dudda Marcel , Dohna-Schwake Christian , Stang Andreas , Bruns Nora
Published: December 2023

Objective

Our study aimed to identify the superior predictor of mortality from International Classification of Diseases 10 (ICD-10) codes among pediatric trauma patients in the German hospital database (GHD), a nationwide database comprising all hospitalizations in the country.

Study design and setting

Hospital admissions of patients aged < 18 years with injury-related ICD-10 codes were selected. The maximum abbreviated injury scale (MAIS) and injury severity score (ISS) were calculated using the ICD-AIS map provided by the Association for the Advancement of Automotive Medicine, which we adjusted to the German modification of the ICD-10 classification. The survival risk ratio was used to calculate the single worst ICD-derived injury (single ICISS) and a multiplicative injury severity score (multiplicative ICISS). The ability to predict mortality of the four above mentioned scores were compared in the selected trauma population and within four clinically relevant subgroups using discrimination and calibration.

Results

Out of 13,992,596 cases < 18 years of age hospitalized between 2014 and 2020, 1,720,802 were trauma patients and ICD-AIS mapping was possible in 1,328,377 cases. Mortality was highest in patients with only one coded injury. Cases with mapping failure (n = 392,425; 22.8 %) were younger and had a higher mortality rate. SRR-derived scores had a better discrimination calibration than ICD-AIS based scores in the overall cohort and all four subgroups (AUC ranges between 0.985 and 0.998 versus 0.886 and 0.972 respectively).

Conclusion

Empirically derived measures of injury severity were superior to ICD-AIS mapped scores in the GHD to predict mortality in pediatric trauma patients. Given the high percentage of mapping failure and high mortality among cases with single coded injury, the single ICISS may be the most suitable measure of injury severity in this group of patients.
Inflammatory bowel disease burden in Asia from 1990 to 2019 and predictions to 2040
Authors: Wang Xingchen , Xiong Jiannan , Ding Zhao , Liu Yueting , Yang Chongguang , Xu Pengfei
Published: December 2023

Background

While the incidence of inflammatory bowel disease (IBD) has stabilized in Western countries since 1990, it is experiencing an upward trend in newly industrializing countries. The Asian region encompasses a multitude of developing countries at varying stages of IBD progression. Therefore, comprehending the current epidemiological characteristics of the disease in this region becomes imperative, enabling countries and locales in Asia to proactively address the evolving IBD burden in the upcoming several decades.

Methods

We analyze variation trends in the burden of IBD in Asia from 1990 to 2019, employing data and methods from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD), and provide projections for future changes in IBD incidence in Asia over the next 20 years.

Results

In 2019, the number of incidence cases of IBD in Asia was 145,561 (95% UI 124,960-170,895), the total number of prevalence cases reached nearly 2 million (95% UI 1.71-2.32), and 13,957 (95% UI 11,898-16,021) patients died of IBD. Meanwhile, the total years lived with disability (YLDs) attributed to IBD amounted to 299,663 (95% UI 198,365-418,635), while the total disability-adjusted life-years (DALYs) rose to 649,760 (95% UI 530,395-783,181). The total number of incidence cases in Asia is projected to reach 179,756 in 2040, with an age-standardized incidence rate of 2.92 per 100,000 population.

Conclusions

The increase in the overall burden of IBD in Asia is primarily driven by population growth and aging, with both incidence and DALYs continuing to rise in most countries. It is imperative for each country to adapt its measures to local conditions, improve prevailing healthcare service patterns, and draw insights from the frontier countries to respond to the evolving epidemic characteristics of IBD.
Predicting the dynamic interaction of intrinsically disordered proteins
Authors: Zheng Yuchuan , Li Qixiu , Freiberger Maria I. , Song Haoyu , Hu Guorong , Zhang Moxin , Gu Ruoxu , Li Jingyuan
Published: December 2023

Intrinsically disordered proteins (IDPs) participate in various biological processes. Interactions involving IDPs are usually dynamic and affected by their inherent conformation fluctuations. Comprehensive characterization of these interactions based on current techniques is challenging. Here, we present GSALIDP, a GraphSAGE-LSTM Network to capture the dynamic nature of IDP-involved interactions and predict their behaviors. This framework models multiple conformations of IDP as a dynamic graph which can effectively describe the fluctuation of its flexible conformation. The dynamic interaction between IDPs is studied and the datasets of IDP conformations and their interactions are obtained through atomistic molecular dynamic (MD) simulations. Residues of IDP are encoded through a series of features, including their frustration. GSALIDP can effectively predict the interaction sites of IDP and the contact residue pairs between IDPs. Its performance in predicting IDP interaction is on par with or even better than the conventional models in predicting the interaction of structural proteins. To the best of our knowledge, this is the first model to extend the protein interaction prediction to IDP-involved interactions.
High-Throughput Screening of the Effects of 90 Xenobiotics on the Simplified Human Gut Microbiota Model (SIHUMIx): A Metaproteomic and Metabolomic Study
Authors: Castañeda-Monsalve Victor , Fröhlich Laura-Fabienne , Haange Sven-Bastiaan , Homsi Masun Nabhan , Rolle-Kampczyk Ulrike , Fu Qiuguo , von Bergen Martin , Jehmlich Nico
Published: December 2023

The human gut microbiota is a complex microbial community with critical functions for the host, including the transformation of various chemicals. While effects on microorganisms has been evaluated using single-species models, their functional effects within more complex microbial communities remain unclear. In this study, we investigated the response of a simplified human gut microbiota model (SIHUMIx) cultivated in an in vitro bioreactor system in combination with 96 deep-well plates after exposure to 90 different xenobiotics, comprising 54 plant protection products and 36 food additives and dyes, at environmentally relevant concentrations. We employed metaproteomics and metabolomics to evaluate changes in bacterial abundances, the production of Short Chain Fatty Acids (SCFAs), and the regulation of metabolic pathways.

Our findings unveiled significant changes induced by 23 out of 54 plant protection products and 28 out of 36 food additives across all three categories assessed. Notable highlights include azoxystrobin, fluroxypyr, and ethoxyquin causing a substantial reduction (log2FC <-0.5) in the concentrations of the primary SCFAs: acetate, butyrate, and propionate. Several food additives had significant effects on the relative abundances of bacterial species; for example, acid orange 7 and saccharin led to a 75% decrease inClostridium butyricum, with saccharin causing an additional 2.5-fold increase inE. colicompared to the control. Furthermore, both groups exhibited up- and down-regulation of various pathways, including those related to the metabolism of amino acids such as histidine, valine, leucine, and isoleucine, as well as bacterial secretion systems and energy pathways like starch, sucrose, butanoate, and pyruvate metabolism.

This research introduces an efficient in vitro technique that enables high-throughput screening of the structure and function of a simplified and well-defined human gut microbiota model against 90 chemicals using metaproteomics and metabolomics. We believe this approach will be instrumental in characterizing chemical-microbiota interactions especially important for regulatory chemical risk assessments.
Cdc13 exhibits dynamic DNA strand exchange in the presence of telomeric DNA
Authors: Nickens David G. , Feng Zhitong , Shen Jiangchuan , Gray Spencer J. , Simmons Robert H. , Niu Hengyao , Bochman Matthew L.
Published: December 2023

Telomerase is the enzyme that lengthens telomeres and is tightly regulated by a variety of means to maintain genome integrity. Several DNA helicases function at telomeres, and we previously found that theSaccharomyces cerevisiaehelicases Hrq1 and Pif1 directly regulate telomerase. To extend these findings, we are investigating the interplay between helicases, single-stranded DNA (ssDNA) binding proteins (ssBPs), and telomerase. The yeast ssBPs Cdc13 and RPA differentially affect Hrq1 and Pif1 helicase activity, and experiments to measure helicase disruption of Cdc13/ssDNA complexes instead revealed that Cdc13 can exchange between substrates. Although other ssBPs display dynamic binding, this was unexpected with Cdc13 due to the reportedin vitrostability of the Cdc13/telomeric ssDNA complex. We found that the DNA exchange by Cdc13 occurs rapidly at physiological temperatures, requires telomeric repeat sequence DNA, and is affected by ssDNA length. Cdc13 truncations revealed that the low-affinity binding site (OB1), which is distal from the high-affinity binding site (OB3), is required for this intermolecular dynamic DNA exchange (DDE). We hypothesize that DDE by Cdc13 is the basis for how Cdc13 “moves” at telomeres to alternate between modes where it regulates telomerase activity and assists in telomere replication.
Un1Cas12f1 and Cas9 gene drive in HSV1: viruses that ‘infect’ viruses
Authors: Yao Qiaorui , Lin Zhuangjie , Lai Keyuan , Zeng Xianying , Lei Guangxiong , Zhang Tongwen , Dai Hongsheng
Published: December 2023

Cas9-based synthetic gene drives have been used for pest control, however, they face high resistance rates, and mitigation strategies developed thus far are difficult to implement. Here, we engineered herpes simplex virus type 1 (HSV1) as a vector for gene drive, generated viruses harboring either the Cas9 or Un1Cas12f1 gene drive, and evaluated these viruses for spreading gene drive and causing resistance. HSV1 supported fast and effective transmission of gene drives, and the Un1Cas12f1 gene drives yielded greater conversion and lower resistance than did the Cas9 gene drives. This positions the Un1Cas12f1 gene drive as a promising alternative, and HSV1 emerges as a dependable and swift platform for gene drive assessment. The gene drive viruses function like pathogens that specifically infect viruses, offering potential applications in attenuating viral infections.
Membrane fusion activity of herpes simplex virus 1 glycoproteins from a hyperfusogenic virus
Authors: Gianopulos Katrina A. , Makio Albina O. , Pritchard Suzanne M. , Cunha Cristina W. , Hull McKenna A. , Nicola Anthony V.
Published: December 2023

Herpes simplex virus 1 (HSV-1) causes significant morbidity and death in humans worldwide. Herpes simplex virus 1 has a complex fusion mechanism that is incompletely understood. The HSV-1 strain ANG has notable fusion and entry activities that distinguish it from wild type. HSV-1 ANG virions fused with the Vero cell surface at 4°C and also entered cells more efficiently at 15°C relative to wild type virions, consistent with a hyperfusogenic phenotype. Understanding the molecular basis for the unique entry and fusion activities of HSV-1 strain ANG will help decipher the HSV fusion reaction and entry process. Sequencing of HSV-1 ANG genes revealed multiple changes in gB, gC, gD, gH, and gL proteins relative to wild type HSV-1 strains. The ANG UL45 gene sequence, which codes for a non-essential envelope protein, was identical to wild type. HSV-1 ANG gB, gD, and gH/gL were necessary and sufficient to mediate cell-cell fusion in a virus-free reporter assay. ANG gB, when expressed with wild type gD and gH/gL, increased membrane fusion, suggesting that ANG gB has hyperfusogenic cell-cell fusion activity. Replacing the wild type gD, gH, or gL with the corresponding ANG alleles did not enhance cell-cell fusion. Wild type gC is proposed to facilitate fusion and entry into epithelial cells by optimizing conformational changes in the fusion protein gB. ANG gC substitution or addition also had no effect on cell-cell fusion. The novel mutations in the ANG fusion and entry glycoproteins provide a platform for dissecting the cascade of interactions that culminate in HSV fusion and entry.
A genome-wide association study suggests new susceptibility loci for primary antiphospholipid syndrome
Authors: Casares-Marfil Desiré , Martínez-Bueno Manuel , Borghi Maria Orietta , Pons-Estel Guillermo ,   PRECISESADS Clinical Consortium, Reales Guillermo , Zuo Yu , Espinosa Gerard , Radstake Timothy , van den Hoogen Lucas L. , Wallace Chris , Guthridge Joel , James Judith A , Cervera Ricard , Meroni Pier Luigi , Martin Javier , Knight Jason S. , Alarcón-Riquelme Marta E. , Sawalha Amr H.
Published: December 2023

Objectives

Primary antiphospholipid syndrome (PAPS) is a rare autoimmune disease characterized by the presence of antiphospholipid antibodies and the occurrence of thrombotic events and pregnancy complications. Our study aimed to identify novel genetic susceptibility loci associated with PAPS.

Methods

We performed a genome-wide association study comprising 5,485 individuals (482 affected individuals) of European ancestry. Significant and suggestive independent variants from a meta-analysis of approximately 7 million variants were evaluated for functional and biological process enrichment. The genetic risk variability for PAPS in different populations was also assessed. Hierarchical clustering, Mahalanobis distance, and Dirichlet Process Mixtures with uncertainty clustering methods were used to assess genetic similarities between PAPS and other immune-mediated diseases.

Results

We revealed genetic associations with PAPS in a regulatory locus within the HLA class II region nearHLA-DRAand inSTAT4with a genome-wide level of significance. 34 additional suggestive genetic susceptibility loci for PAPS were also identified. The disease risk allele in the HLA class II locus is associated with overexpression ofHLA-DRB6,HLA-DRB9,HLA-DPB2,HLA-DQA2andHLA-DQB2, and is independent of the association between PAPS andHLA-DRB1*1302. Functional analyses highlighted immune and nervous system related pathways in PAPS-associated loci. The comparison with other immune-mediated diseases revealed a close genetic relatedness to neuromyelitis optica, systemic sclerosis, and Sjögren’s syndrome, suggesting colocalized causal variations close toSTAT4,TNPO3, andBLK.

Conclusions

This study represents a comprehensive large-scale genetic analysis for PAPS and provides new insights into the genetic basis and pathophysiology of this rare disease.
Organizational digital transformation: from evolution to future trends
Authors: Omol Edwin Juma
Published: December 2023

Purpose

This article explores the emergence of organizational digital transformation in the rapidly advancing technological era. It discusses the origins, driving forces, strategies, challenges and broader implications.

Design/methodology/approach

The article employs a scoping review methodology that synthesizes knowledge from the existing literature, research, case studies and other relevant sources.

Findings

The findings underscore the pivotal role that organizational digital transformation plays in an era of relentless technological advancement. Leadership, organizational culture and technological enablers are identified as crucial drivers of innovation and competitiveness within organizations. The article also emphasizes ethics as a crucial element of digital transformation, focusing in particular on concerns about data privacy and the morality of artificial intelligence. Additionally, the author talks about anticipated future trends that are anticipated to influence the future of digital transformation, such as the growing influence of artificial intelligence, the trend toward hyper-personalization and the emergence of quantum computing.

Research limitations/implications

The assessment has failed to provide recommendations for the actual implementation because it has mainly concentrated on conceptual and strategic aspects. Furthermore, it does not clearly define the criteria for choosing real-world examples, which limits the representation of the different industries, size ranges of organizations and outcomes associated with digital transformation.

Practical implications

The article stresses the significance of paying attention to the forces driving digital transformation while navigating ethical and societal concerns. In addition to highlighting the importance of anticipating future trends for strategic planning in the rapidly changing digital landscape, it emphasizes the advantages as incentives for organizations to invest in digital initiatives.

Social implications

The investigation demonstrates how technology contributes to progress while posing complex ethical and change management issues. In light of increased connectivity, data analytics and artificial intelligence, it highlights the crucial need for societal adaptability and highlights the crucial role that cooperative human–machine coexistence plays in responsible development and transformative societal evolution.

Originality/value

The article stands out because it examines organizational digital transformation in-depth while considering its historical roots, ethical implications and future prospects. It is a priceless contribution to the field because real-world case studies and a scoping review provide a distinctive viewpoint and a comprehensive view of the effects of digital transformation on organizations and society.
Gattani Industries: growth strategy for India
Authors: Mehdi Mokhalles Mohammad , Nafees Lubna , Sarma Tridib Ranjan , Sultana Farnaz
Published: December 2023

Learning outcomes

After completion of the case study, students will be able to understand general and specific challenges associated with carrying on a family business that faces market challenges including stiff competition from existing and newer players, understand the plywood manufacturing process and its supply chain management, understand the businesses operating in an organized versus the unorganized market, comprehend the marketing strategies adopted and identify a reasonable solution to address the challenges associated with the operations of a business.

Case overview/synopsis

This case study focuses on Gattani Industries (a plywood manufacturing company) located in the northeastern region of the Indian state of Assam. Headquartered at Cinnamara industrial zone of Jorhat district, Assam, the company began its operation in 1992 under the leadership of Makhan Gattani (Director). Gattani Industries catered to both residential and commercial demand. Its clients included the departments of central and state governments in India, public sector undertakings and civil contractors. The company had a wider distribution network across the country and adopted the one- and two-level marketing channels to reach consumers. It aimed to sell its products through dealers across the cities in India. However, in December 2019, Gattani faced the challenge of developing a growth strategy to overcome competition and use the upcoming market opportunities for business growth in the diverse and complex environment that existed in the country.

Complexity academic level

This case study is designed for use in graduate or undergraduate programs. This case study can be used in strategy, supply chain and marketing courses at Bachelor of Business Administration and Master of Business Administration levels.

Supplementary material

Teaching notes are available for educators only.

Subject code

CSS11: Strategy.
Transitioning beyond single-use plastic drinks cups: an emergent social marketing case study in Scotland
Authors: Carrigan Marylyn , Wells Victoria , Mackay Kerry
Published: December 2023

Purpose

This study aims to investigate whether consumers and small businesses can transition from disposable to reusable coffee cups, using a community social marketing intervention, led by a Social Purpose Organisation.

Design/methodology/approach

An emergent case study approach using multiple sources of data developed an in-depth, multifaceted, real-world context evaluation of the intervention. The methodology draws on citizen science “messy” data collection involving multiple, fragmented sources.

Findings

Moving from single-use cups to reusables requires collective commitment by retailers, consumers and policymakers, despite the many incentives and penalties applied to incentivise behaviour change. Difficult post-COVID economics, austerity and infrastructure gaps are undermining both reusable acceptance and interim solutions to our dependence upon disposables.

Research limitations/implications

Although the non-traditional methodology rendered gaps and omissions in the data, the citizen science was democratising and inclusive for the community.

Practical implications

Our practical contribution evaluates a whole community intervention setting to encourage reusable cups, integrating multiple stakeholders, in a non-controllable, non-experimental environment in contrast to previous research. This paper demonstrates how small community grants can foster impactful collaborative partnerships between an SPO and researchers, facilitate knowledge-exchange beyond the initial remit and provide a catalyst for possible future impact and outcomes.

Originality/value

To assess the impact at both the outcome and the process level of the intervention, we use Pawson and Tilley’s realist evaluation theory – the Context Mechanism Outcome framework. The methodological contribution demonstrates the process of citizen science “messy” data collection, likely to feature more frequently in future social science research addressing climate change and sustainability challenges.
Effective measures to bolster the deployment of indoor environmental quality (IEQ) principles in building design: a focus on quantity surveying (QS) firms in Nigeria
Authors: Oke Ayodeji Emmanuel , Aliu John , Agbaje Doyin Helen , Jamir Singh Paramjit Singh , Alade Kehinde Temitope , Samsurijan Mohamad Shaharudin
Published: December 2023

Purpose

Research on measures to strengthen the implementation of indoor environmental quality (IEQ) principles has been scarce in developing countries such as Nigeria. Hence, this study sought to identify and assess the crucial measures for encouraging the adoption of IEQ principles in the Nigerian construction industry, specifically from the viewpoint of quantity surveyors.

Design/methodology/approach

To accomplish this objective, a quantitative research methodology was employed, utilizing a well-structured questionnaire distributed to quantity surveying (QS) firms in Nigeria. The collected data were examined using a range of statistical techniques such as frequencies, percentages, mean item scores (MISs), the Kruskal–Wallis test and exploratory factor analysis.

Findings

The top five ranked measures were as follows: offer financial incentives and tax breaks, develop educational materials and resources, establish clear and accessible reporting mechanisms, develop awards and recognition programs and provide advocacy and awareness campaigns. Factor analysis led to the categorization of the identified measures into four primary clusters: education and training, policy and regulation, incentivization and recognition and collaboration and networking. Consequently, these clusters were renamed the EPIC (Education and training, Policy and regulation, Incentivization and recognition and Collaboration and networking) framework, with each first letter representing a significant measure for fostering the adoption of IEQ principles.

Practical implications

Consequently, this study offers a robust foundation for understanding and implementing measures to enhance the adoption of IEQ principles within the Nigerian construction industry, ultimately benefiting stakeholders and improving the quality of built environments.

Originality/value

The EPIC framework designed in this study offers valuable insights for policymakers, construction industry professionals and other stakeholders interested in promoting IEQ principles, which can potentially lead to healthier, more comfortable and more sustainable built environments in Nigeria and beyond.
Artisan entrepreneurship: influence and network in the development of sustainable strategies in cross-border low-density territories through a Quintuple Helix paradigm
Authors: Rodrigues Alex Olivier , Marques Carla Susana , Ramadani Veland
Published: December 2023

Purpose

The purpose of this study is, from the perspective of artisan entrepreneurship (AE), to understand how professional and higher education institutions, local authorities, local and cross-border cultural entities and tourism stakeholders perceive AE by collaborating in a network to develop innovative and sustainable strategies, using the Quintuple Helix innovation model.

Design/methodology/approach

Using a qualitative approach, 34 semi-structured interviews were carried out with organisations by emailing them a Google Form. The organisations interviewed were from the north-east of Portugal (Bragança, Miranda do Douro, Mogadouro, Vimioso and Vinhais) and the north of Spain (Zamora Province). The data collected was subjected to content and lexical analysis using the computerised lexical analysis software IRaMuTeQ.

Findings

AE is seen as the representation of a culture where traditional crafts are the identity of a region. The practical and political implications for decision makers in the Quintuple Helix can be seen in the definition of strategies and proposals that should leverage and define regional and cross-border policies, leveraging the need for networking to define concrete measures and programmes for support and training in entrepreneurship and AE, as well as the creation and/or standardisation of existing support networks.

Originality/value

To the best of the authors’ knowledge, this work is the first study to address and deal with the issue of AE by understanding how professional and higher education institutions, local authorities, local and cross-border cultural entities perceive AE and collaborate in a network to develop innovative and sustainable strategies, through the paradigm of the Quintuple Helix model. It also combines a content analysis and a lexical analysis using computerised lexical analysis software – IRaMuTeQ.
Africa rising: turning sporting potential into success
Authors: Agyemang Kwame J.A. , Ayenor Nana Ama , Hammond Marilyn , Bortey Joel Nii Borte
Published: December 2023

Purpose

The purpose of this essay is to provide a better understanding of Africa's sport industry and demonstrate how the industry can be transformed.

Design/methodology/approach

To do so, the authors rely on their varied experiences within Africa's sport ecosystem. This includes reflections based on consuming sport in Africa, studying the sport business landscape, and first-hand experiences working inside African sport organizations.

Findings

The authors find that systemic challenges restrict the growth of Africa's sport industry; however, they maintain there are also reasons to be optimistic about the prospects of the industry.

Research limitations/implications

While not an exhaustive list, the authors' commentary defines various research opportunities for scholars interested in both better understanding and improving Africa's sport industry.

Practical implications

The stated challenges and proposed strategies have the potential to inform decision-makers within Africa's sport ecosystem.

Social implications

Crucial to the continued growth and development of the continent, the authors propose that investments in sport can drive broader economic and social development beyond sport.

Originality/value

The authors address the dearth of academic literature on Africa's sport industry, while also inviting more researchers to undertake research agendas that enhance Africa.