bluuebunny/crossref_metadata_2025 huggingface dataset:
End-to-end AI framework for interpretable prediction of molecular and crystal properties
Authors: Park Hyun , Zhu Ruijie , Huerta E A , Chaudhuri Santanu , Tajkhorshid Emad , Cooper Donny
Published: May 2023

We introduce an end-to-end computational framework that allows for hyperparameter optimization using the DeepHyper library, accelerated model training, and interpretable AI inference. The framework is based on state-of-the-art AI models including CGCNN, PhysNet, SchNet, MPNN, MPNN-transformer, and TorchMD-NET. We employ these AI models along with the benchmark QM9, hMOF, and MD17 datasets to showcase how the models can predict user-specified material properties within modern computing environments. We demonstrate transferable applications in the modeling of small molecules, inorganic crystals and nanoporous metal organic frameworks with a unified, standalone framework. We have deployed and tested this framework in the ThetaGPU supercomputer at the Argonne Leadership Computing Facility, and in the Delta supercomputer at the National Center for Supercomputing Applications to provide researchers with modern tools to conduct accelerated AI-driven discovery in leadership-class computing environments. We release these digital assets as open source scientific software in GitLab, and ready-to-use Jupyter notebooks in Google Colab.
Synchronizing dynamical systems: Their groupoids and 𝐶*-algebras
Authors: Deeley Robin , Stocker Andrew
Published: May 2023

Building on work of Ruelle and Putnam in the Smale space case, Thomsen defined the homoclinic and heteroclinic

C
∗

C^\ast

-algebras for an expansive dynamical system. In this paper we define a class of expansive dynamical systems, called synchronizing dynamical systems, that exhibit hyperbolic behavior almost everywhere. Synchronizing dynamical systems generalize Smale spaces (and even finitely presented systems). Yet they still have desirable dynamical properties such as having a dense set of periodic points. We study various

C
∗

C^\ast

-algebras associated with a synchronizing dynamical system. Among other results, we show that the homoclinic algebra of a synchronizing system contains an ideal which behaves like the homoclinic algebra of a Smale space.
The Tetrahymena bcd1 mutant implicates endosome trafficking in ciliate, cortical pattern formation
Authors: Cole Eric S. , Maier Wolfgang , Joachimiak Ewa , Jiang Yu-yang , Lee Chinkyu , Collet Erik , Chmelik Carl , Romero Daniel P. , Chalker Douglas , Alli Nurudeen K. , Ruedlin Tina M. , Ozzello Courtney , Gaertig Jacek
Published: May 2023

In the ciliate Tetrahymena thermophila, the BCD1 pattern-gene encodes a Beige-BEACH-domain protein that defines cortical organelle dimensions through regulated endocytic activity. Tetrahymena cells homozygous for a bcd1 loss-of-function mutation exhibit supernumerary cortical organelles including oral apparatuses, cytoprocts and contractile vacuole pores. Elements of the broadened cortical domain phenotype can be phenocopied by disrupting clathrin-mediated endocytosis, suggesting that exocytic membrane delivery is balanced by endocytic retrieval of cortical pattern determinants..
Extracellular Vesicles Derived From Hypoxia-Treated Human Adipose Stem Cells Increase Proliferation and Angiogenic Differentiation in Human Adipose Stem Cells
Authors: Li Wei , Chen Xu , Zou Feng , He Xiaotong
Published: May 2023

Background

Adipose-derived stem cells (ADSCs) are crucial in cell-assisted lipotransfer (CAL). ADSC-derived exosomes could improve the survival of CAL. Almost all relevant research now ignores ADSCs in favor of studying the proangiogenic potential of extracellular vesicles (EVs) on human umbilical vein endothelial cells (HUVECs).

Objectives

Given the significance of ADSCs in CAL, the authors sought to verify that EVs from ADSCs under hypoxia treatment can enhance the angiogenic potential of ADSCs.

Methods

EVs were harvested from human ADSCs (hADSCs) under normoxia and hypoxia. A Cell Counting Kit-8 (CCK-8) assay was used to measure the proliferation of hADSCs. By examining the expression of CD31, vascular endothelial growth factor receptor 2, and vascular endothelial growth factor, the pro-angiogenic differentiation potential was assessed. Moreover, a tube formation experiment was carried out to evaluate the pro-angiogenic differentiation potential.

Results

Hypoxic EVs showed more significant pro-proliferative and pro-angiogenic potential. Angiogenesis was more vigorous in hADSCs treated with hypoxic EVs than in those treated with nomorxic EVs. The hADSCs treated with hypoxic EVs expressed higher angiogenic markers, according to real-time polymerase chain reaction (RT-PCR) and Western blot analysis, which revealed more angiogenic marker expression in hypoxic EV–treated hADSCs. The same result was demonstrated by tube formation on Matrigel in vitro.

Conclusions

Hypoxic EVs significantly increased the proliferation and angiogenic differentiation potential of hADSCs. Hypoxic EV–treated ADSCs may be beneficial to CAL and prevascularized tissue-engineered constructs.
Risk stratification for the detection of metachronous polyps after bowel screening polypectomy: clinical outcomes from the Integrated Technologies for Improved Polyp Surveillance (INCISE) study cohort
Authors: Johnstone Mark S , Stoops Reiss , Lynch Gerard , Hay Jennifer , Jawny Jakub , Sloan William , Edwards Joanne , McSorley Stephen T
Published: May 2023

Background

After colorectal polypectomy, 20–50 per cent of patients develop metachronous polyps and some have increased colorectal cancer risk. British Society of Gastroenterology (BSG) 2020 guidelines recommend surveillance colonoscopy for high-risk patients based on index pathology. The aim of this study was to evaluate metachronous lesion outcome using BSG 2020 criteria.

Methods

A retrospective, multicentred study was conducted including patients who had polypectomy during screening colonoscopy (2009–2016) followed by surveillance. Demographics, index pathology, and BSG 2020 risk criteria were compared with regard to metachronous lesion pathology (non-advanced versus advanced lesions) and timing of detection (early versus late). Advanced lesions were defined as adenomas/serrated polyps greater than or equal to 10 mm, high-grade dysplasia, serrated polyps with dysplasia, or colorectal cancer, and late lesions those detected greater than 2 years after the index procedure.

Results

Of 3090 eligible patients, 2643 were included. Among these, retrospective BSG 2020 application would have excluded 51.5 per cent from surveillance. After a median of 36 months, the advanced polyp/colorectal cancer rate in BSG 2020 high-risk patients was 16.3 versus 13.0 per cent in low-risk patients. Older age (P = 0.008) correlated with advanced metachronous lesions. Male sex, greater than five polyps, and BSG 2020 high-risk criteria correlated with non-advanced and advanced lesions (P < 0.001). Older age (P < 0.001), villous features (P = 0.006), advanced index polyp (P = 0.020), and greater than five polyps (P < 0.001) correlated with early metachronous lesions. Male sex and BSG 2020 high-risk criteria correlated with early and late lesions (P < 0.001). On multivariable regression, increased polyp number (odds ratio (OR) 1.15 (95 per cent c.i. 1.07 to 1.25); P < 0.001) and villous features (OR 1.49 (95 per cent c.i. 1.05 to 2.10); P = 0.025) independently correlated with early advanced lesions. The rate of non-advanced and advanced metachronous polyps was higher in BSG 2020 high- versus low-risk patients (44.4 versus 35.4 per cent for non-advanced and 15.7 versus 11.8 per cent for advanced; P < 0.001), but the colorectal cancer rate was similar (0.6 versus 1.2 per cent). However, when examining only lesions detected greater than 2 years after the index colonoscopy in high- versus low-risk patients, no significant differences were observed (P = 0.140).

Conclusion

BSG 2020 criteria correlated with metachronous polyps, but did not differentiate advanced and non-advanced lesions and were not predictive of late lesions.
In Vivo Evaluation of the Pharmacokinetic Interaction between Levothyroxine and Amiodarone in Rat Plasma: Evaluation of Importance of Therapeutic Drug Monitoring during Co-Therapy
Authors: AlSawy Norhan S , ElKady Ehab F , Mostafa Eman A
Published: May 2023

Amiodarone-induced thyrotoxicosis (AIT) is a common condition in patients who are receiving amiodarone for cardiac arrhythmia. This risk is elevated in iodine-deficient regions. Levothyroxine is the standard treatment for patients with hypothyroidism. This investigation is concerned with the evaluation of the possible pharmacokinetic interaction between amiodarone and levothyroxine upon co-therapy in rats and to investigate the cause of thyrotoxicosis. A selective, sensitive and precise RP-HPLC method was developed for the simultaneous determination of levothyroxine and amiodarone in rat plasma. A stationary phase of C18 Xterra RP column and a mobile phase consisting of acetonitrile: acidified water with 0.1% trifluoracetic acid (pH = 4.8) with gradient elution were used. The experiment was conducted at ambient temperature with flow rate of 1.5 mL/min for the chromatographic separation and quantitation of the investigated drugs. Protein precipitation with methanol was applied for the analysis of the two drugs in rat plasma. The method was linear over concentration range of 5–200 μg/mL for both levothyroxine and amiodarone. The European Medicines Agency guideline was applied for the validation of the developed bioanalytical method. The method was successfully applied to in vivo pharmacokinetic study in which levothyroxine and amiodarone were quantified in plasma of rats after receiving an oral dose of levothyroxine and amiodarone. After the calculation of the pharmacokinetic parameters, a statistical analysis was performed to elucidate the existence of significant difference between test and control groups in rats. The combination of levothyroxine and amiodarone significantly decreased levothyroxine bioavailability in rats, making the therapeutic drug monitoring mandatory in patients receiving levothyroxine and amiodarone. In addition, the increased clearance of levothyroxine upon the co-administration with amiodarone may explain the reported hypothyroidism.
Research protocol for the Paraesophageal hernia symptom tool, a prospective multi-center cohort study to identify the need and threshold for surgery and assess the symptom response to surgery
Authors: Menon Nainika , Guidozzi Nadia , Chidambaram Swathikan , Puri Aiysha , Sounderajah Viknesh , Ferri Lorenzo , Griffiths Ewen A , Low Donald , Maynard Nick , Mueller Carmen , Pera Manuel , van Berge Henegouwen Mark I , Watson David I , Zaininotto Giovanni , Hanna George B , Markar Sheraz R
Published: May 2023

Large hiatus hernias with a significant paraesophageal component (types II–IV) have a range of insidious symptoms. Management of symptomatic hernias includes conservative treatment or surgery. Currently, there is no paraesophageal hernia disease-specific symptom questionnaire. As a result, many clinicians rely on the health-related quality of life questionnaires designed for gastro-esophageal reflux disease (GORD) to assess patients with hiatal hernias pre- and postoperatively. In view of this, a paraesophageal hernia symptom tool (POST) was designed. This POST questionnaire now requires validation and assessment of clinical utility. Twenty-one international sites will recruit patients with paraesophageal hernias to complete a series of questionnaires over a five-year period. There will be two cohorts of patients—patients with paraesophageal hernias undergoing surgery and patients managed conservatively. Patients are required to complete a validated GORD-HRQL, POST questionnaire, and satisfaction questionnaire preoperatively. Surgical cohorts will also complete questionnaires postoperatively at 4–6 weeks, 6 months, 12 months, and then annually for a total of 5 years. Conservatively managed patients will repeat questionnaires at 1 year. The first set of results will be released after 1 year with complete data published after a 5-year follow-up. The main results of the study will be patient’s acceptance of the POST tool, clinical utility of the tool, assessment of the threshold for surgery, and patient symptom response to surgery. The study will validate the POST questionnaire and identify the relevance of the questionnaire in routine management of paraesophageal hernias.
Navigating premature rupture of the expandable sheath delivery system during elective transfemoral transcatheter aortic valve implantation: a case report
Authors: Chapman Andrew R , Russell-Dalton Anastasia , Holland James , Flapan Andrew D
Published: May 2023

Background

Transcatheter aortic valve implantation (TAVI) has revolutionised the treatment of severe aortic stenosis, but is still associated with a risk of major vascular complication.

Case summary

An elective transfemoral TAVI was undertaken for severe aortic stenosis. During delivery of a 26mm Sapien S3 valve, the delivery system sheath (eSheath) split prematurely. The valve could not be advanced, and lay parallel to the sheath body. Following advice, an attempt was made to remove the system en bloc but this was unsuccessful. After careful consideration of alternative options, the valve was advanced with reasonable force and the case was completed successfully. The femoral artery was closed with parclose sutures without major vascular complication.

Discussion

Early recognition of a split sheath with effective communication between lab team members and the manufacturer allowed us to successfully navigate this case, with a good outcome for our patient.
Massive myocardial infiltration by primary anaplastic T-cell lymphoma: a case report
Authors: Cumitini Luca , Rossi Lidia , Giubertoni Ailia , Patti Giuseppe
Published: May 2023

Background

Myocardial infiltration by primary cardiac neoplasm is a rare entity, providing diagnostic and therapeutic challenges. The pathological spectrum includes more frequently benign forms. Refractory heart failure, pericardial effusion, and arrhythmias due to infiltrative mass are the most common clinical manifestations.

Case summary

We describe the case of a 35-year-old man complaining of shortness of breath and weight loss in the last 2 months. A previous acute myeloid leukaemia treated with allogenic bone marrow transplant was reported. Transthoracic echocardiography revealed an apical thrombus in the left ventricle, with inferior and septal hypokinesia conditioning a mildly reduced ejection fraction, circumferential pericardial effusion, and abnormal right ventricular thickening. Cardiac magnetic resonance confirmed diffuse thickening of the right ventricular free wall due to myocardial infiltration. Positron emission tomography showed the presence of neoplastic tissue with increased metabolic activity. A pericardiectomy was performed showing a widespread cardiac neoplastic infiltration. Histopathological analysis done on right ventricular pathological samples obtained during cardiac surgery revealed the presence of a rare and aggressive cardiac anaplastic T-cell non-Hodgkin lymphoma. Few days after the operation, the patient developed refractory cardiogenic shock and unluckily died before initiating an adequate antineoplastic therapy.

Discussion

Primary cardiac lymphoma is not frequent, and the lack of specific symptoms makes the diagnosis extremely challenging and often limited to autopsy findings. Our case highlights the importance of an appropriate diagnostic algorithm, requiring non-invasive multimodality assessment imaging and then invasive cardiac biopsy. This approach may allow an early diagnosis and an adequate therapy for this otherwise fatal pathology.
Creatinine-based European Kidney Function Consortium equation is superior to the Chronic Kidney Disease Epidemiology Collaboration equation for mortality risk stratification in general non-Black population
Authors: Lu Xinyi , Gao Rongrong , Liao Shengen
Published: May 2023

Aims

A recent study demonstrated that the new modified estimated glomerular filtration rate (eGFR) equation proposed by the European Kidney Function Consortium (EKFC) was more accurate and precise than the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. This study aimed to compare the prognostic values of these two creatinine-based equations with regard to all-cause and cardiovascular mortality in general non-Black population.

Methods and results

A population-based cohort study was conducted using data from the National Health and Nutrition Examination Survey database from 1999 to 2018, and 38 983 non-Black individuals aged 20 years or older without a history of dialysis were enrolled. Among 38 983 participants, 6103 deaths occurred after a median follow-up duration of 112 months, of which 1558 deaths were due to cardiovascular causes. There were U-shaped relations between the eGFR values and the risk of all-cause and cardiovascular mortality. The areas under the curves for the EKFC were significantly higher than those for the CKD-EPI equation for all-cause and cardiovascular mortality. The integrated discrimination improvement for the EKFC equation compared with the CKD-EPI equation was 2.40% and 1.26% for 10-year all-cause and cardiovascular mortality; the net reclassification improvement for the EKFC equation compared with the CKD-EPI equation was 8.67% and 11.13% for 10-year all-cause mortality and cardiovascular mortality.

Conclusion

Creatinine-based EKFC equation outperformed the CKD-EPI equation for the prediction of long-term all-cause and cardiovascular mortality in the general non-Black population.
Heterogeneous Effects of Women's Schooling on Fertility, Literacy and Work: Evidence from Burundi's Free Primary Education Policy
Authors: Wild Frederik , Stadelmann David
Published: May 2023

This article investigates the effect of women's schooling on fertility as well as on associated mechanisms by leveraging Burundi's free primary education policy (FPE) of 2005 as a natural experiment. Exogenous variation in schooling is identified through a fuzzy regression discontinuity design. Our results show that educational attainment was positively influenced by Burundi's FPE for women situated at all wealth levels. However, the relevant downstream effects of schooling—measured by fertility, literacy and work outcomes—reveal heterogenous treatment effects which are moderated by women's household wealth. While poor women profit in terms of increases in literacy (6.7 percentage-point increase for each year of policy-induced schooling), remunerated employment opportunities (5.7 percentage-point increase), as well as a reduction in desired and actual fertility outcomes (6.9 percentage-point reduction in teenage childbirth), none of these effects of additional education are observed for women from the wealthier households of our sample. The evidence of such a marked heterogeneity contributes to the growing literature examining the nexus between education and fertility in developing countries and helps to evaluate under which conditions the literature's findings may generalize.
Molecular mechanisms protecting centromeres from self-sabotage and implications for cancer therapy
Authors: Nassar Rim , Thompson Lily , Fouquerel Elise
Published: May 2023

Centromeres play a crucial role in DNA segregation by mediating the cohesion and separation of sister chromatids during cell division. Centromere dysfunction, breakage or compromised centromeric integrity can generate aneuploidies and chromosomal instability, which are cellular features associated with cancer initiation and progression. Maintaining centromere integrity is thus essential for genome stability. However, the centromere itself is prone to DNA breaks, likely due to its intrinsically fragile nature. Centromeres are complex genomic loci that are composed of highly repetitive DNA sequences and secondary structures and require the recruitment and homeostasis of a centromere-associated protein network. The molecular mechanisms engaged to preserve centromere inherent structure and respond to centromeric damage are not fully understood and remain a subject of ongoing research. In this article, we provide a review of the currently known factors that contribute to centromeric dysfunction and the molecular mechanisms that mitigate the impact of centromere damage on genome stability. Finally, we discuss the potential therapeutic strategies that could arise from a deeper understanding of the mechanisms preserving centromere integrity.
Feeling sleepy? stop driving—awareness of fall asleep crashes
Authors: Anderson Clare , Cai Anna W T , Lee Michael L , Horrey William J , Liang Yulan , O’Brien Conor S , Czeisler Charles A , Howard Mark E
Published: May 2023

Study Objectives

To examine whether drivers are aware of sleepiness and associated symptoms, and how subjective reports predict driving impairment and physiological drowsiness.

Methods

Sixteen shift workers (19–65 years; 9 women) drove an instrumented vehicle for 2 hours on a closed-loop track after a night of sleep and a night of work. Subjective sleepiness/symptoms were rated every 15 minutes. Severe and moderate driving impairment was defined by emergency brake maneuvers and lane deviations, respectively. Physiological drowsiness was defined by eye closures (Johns drowsiness scores) and EEG-based microsleep events.

Results

All subjective ratings increased post night-shift (p < 0.001). No severe drive events occurred without noticeable symptoms beforehand. All subjective sleepiness ratings, and specific symptoms, predicted a severe (emergency brake) driving event occurring in the next 15 minutes (OR: 1.76–2.4, AUC > 0.81, p < 0.009), except “head dropping down”. Karolinska Sleepiness Scale (KSS), ocular symptoms, difficulty keeping to center of the road, and nodding off to sleep, were associated with a lane deviation in the next 15 minutes (OR: 1.17–1.24, p<0.029), although accuracy was only “fair” (AUC 0.59–0.65). All sleepiness ratings predicted severe ocular-based drowsiness (OR: 1.30–2.81, p < 0.001), with very good-to-excellent accuracy (AUC > 0.8), while moderate ocular-based drowsiness was predicted with fair-to-good accuracy (AUC > 0.62). KSS, likelihood of falling asleep, ocular symptoms, and “nodding off” predicted microsleep events, with fair-to-good accuracy (AUC 0.65–0.73).

Conclusions

Drivers are aware of sleepiness, and many self-reported sleepiness symptoms predicted subsequent driving impairment/physiological drowsiness. Drivers should self-assess a wide range of sleepiness symptoms and stop driving when these occur to reduce the escalating risk of road crashes due to drowsiness.
Rhizosphere and Root Community Analysis of Oomycetes Associated with Poor Alfalfa (Medicago sativa) Seedling Establishment
Authors: Larsen Leta J. , Schlatter Daniel C. , Nimpoeno Jason , Hines-Snider Carla , Samac Deborah A.
Published: May 2023

Alfalfa ( Medicago sativa) seeds planted in cold, wet soil are prone to seed rot, pre- and postemergence damping-off, and seedling root rot. These diseases reduce initial stand density and affect forage yields and winter survival when root systems are stunted by infection. Successful management depends on identifying the causal agents but isolation in pure culture is time consuming and may fail to recover slow-growing organisms or those requiring special growth conditions. Here, the oomycetes in rhizosphere soil and roots from eight locations with a history of poor alfalfa establishment were identified by amplicon sequence analysis. Seedling bioassays were done with bulk soil and quantitative PCR (qPCR) assays were done using DNA from bulk soil, rhizosphere soil, and the root tissue for Aphanomyces euteiches, Phytophthora medicaginis, Pythium irregulare, P. sylvaticum, and P. ultimum var. ultimum. In the root tissue and rhizosphere, A. euteiches was the dominant taxon, followed by Phytophthora medicaginis and P. sansomeana, a broad-host-range pathogen not previously known to infect alfalfa. Pythium inflatum and Globisporangium perplexum were also significantly overrepresented in roots at five of the eight locations, indicating that these taxa are commonly enriched in alfalfa roots but had not previously been identified as alfalfa pathogens. The qPCR assays of bulk soil showed that A. euteiches and Phytophthora medicaginis were unevenly distributed in the plots and low concentrations of the pathogens led to high levels of root rot disease. These results support development of cultivars with high levels of resistance to the most common oomycete pathogens.
Hu'po Anshen decoction promotes fracture healing in mice with traumatic brain injury through BMP2‐COX2‐ATF4 signaling pathway
Authors: Ding WeiHang , Ji RuiQing , Yao Sai , Ruan PengFei , Ye Fei , Lou XiuLong , Ni LiPing , Ji YuChi , Chen Jie , Ji WeiFeng
Published: May 2023

Hu'po Anshen decoction (HPASD), a traditional Chinese medicine used to treat concussion and fracture, could regulate the expression of bone morphogenetic protein 2 (BMP2). However, whether HPASD affects the fracture healing of traumatic brain injury (TBI) combined with a fracture through BMP2 and its downstream signals remains obscure. The chondrocyte‐specific BMP2 conditional knockout mice and chondrocyte‐specific cyclooxygenase‐2 (COX2) overexpression mice were generated. BMP2 conditional knockout mice were treated with fracture surgery, fracture combined with TBI, or fracture combined with TBI followed by different doses of HPASD (2.4, 4.8, and 9.6 g/kg), respectively. TBI was induced by Feeney's weight‐drop technique. The fracture callus formation and fracture sites were determined by X‐ray, micro‐CT, and histological analyses. The expressions of chondrocyte‐, osteoblast‐, and BMP2/COX2 signal‐related targets were determined by quantitative reverse transcription‐polymerase chain reaction (qRT‐PCR) and western blot assays. The specific absence of BMP2 in chondrocytes led to the prolonged formation of cartilage callus, a delay in the osteogenesis initiation and the downregulation of RUNX2, Smad1/5/9, EP4, ERK1/2, RSK2, ATF4. Overexpression of COX2 partially reverses the effects of chondrocyte‐specific BMP2 knockout mice. HPASD promoted cartilage callus formation and osteogenesis initiation, as accompanied by upregulated expression levels of RUNX2, Smad1/5/9, EP4, ERK1/2, RSK2, and ATF4 in a time‐dependent and concentration‐dependent manner in chondrocyte‐specific BMP2 knockout mice. Overall, our findings demonstrated that HPASD induced COX2 transcription through the BMP2‐Smad1/5/9‐RUNX2 axis, and then affected fracture healing through the COX2‐mediated EP4‐ERK1/2‐RSK2‐ATF4 axis.
A LGR5 reporter pig model closely resembles human intestine for improved study of stem cells in disease
Authors: Schaaf Cecilia R. , Polkoff Kathryn M. , Carter Amber , Stewart Amy S. , Sheahan Breanna , Freund John , Ginzel Joshua , Snyder Joshua C. , Roper Jatin , Piedrahita Jorge A. , Gonzalez Liara M.
Published: May 2023

Intestinal epithelial stem cells (ISCs) are responsible for intestinal epithelial barrier renewal; thereby, ISCs play a critical role in intestinal pathophysiology research. While transgenic ISC reporter mice are available, advanced translational studies lack a large animal model. This study validates ISC isolation in a new porcine Leucine Rich Repeat Containing G Protein‐Coupled Receptor 5 (LGR5) reporter line and demonstrates the use of these pigs as a novel colorectal cancer (CRC) model. We applied histology, immunofluorescence, fluorescence‐activated cell sorting, flow cytometry, gene expression quantification, and 3D organoid cultures to whole tissue and single cells from the duodenum, jejunum, ileum, and colon of LGR5‐H2B‐GFP and wild‐type pigs. Ileum and colon LGR5‐H2B‐GFP, healthy human, and murine biopsies were compared by mRNA fluorescent in situ hybridization (FISH). To model CRC, adenomatous polyposis coli (APC) mutation was induced by CRISPR/Cas9 editing in porcine LGR5‐H2B‐GFP colonoids. Crypt‐base, green fluorescent protein (GFP) expressing cells co‐localized with ISC biomarkers. LGR5‐H2B‐GFPhi cells had significantly higher LGR5 expression (p < .01) and enteroid forming efficiency (p < .0001) compared with LGR5‐H2B‐GFPmed/lo/neg cells. Using FISH, similar LGR5, OLFM4, HOPX, LYZ, and SOX9 expression was identified between human and LGR5‐H2B‐GFP pig crypt‐base cells. LGR5‐H2B‐GFP/APCnull colonoids had cystic growth in WNT/R‐spondin‐depleted media and significantly upregulated WNT/β‐catenin target gene expression (p < .05). LGR5+ ISCs are reproducibly isolated in LGR5‐H2B‐GFP pigs and used to model CRC in an organoid platform. The known anatomical and physiologic similarities between pig and human, and those shown by crypt‐base FISH, underscore the significance of this novel LGR5‐H2B‐GFP pig to translational ISC research.
Clinical Improvement After Lumbar Fusion
Authors: Shaikh Hashim J.F. , Cady-McCrea Clarke I. , Menga Emmanuel N. , Haddas Ram , Molinari Robert N. , Mesfin Addisu , Rubery Paul T. , Puvanesarajah Varun
Published: May 2023

Study Design.

Retrospective review of a single institution cohort.

Objective.

The goal of this study is to identify features that predict delayed achievement of minimum clinically important difference (MCID) following elective lumbar spine fusion using Patient-Reported Outcomes Measurement Information System (PROMIS) surveys.

Summary of Background Data.

Preoperative prediction of delayed recovery following lumbar spine fusion surgery is challenging. While many studies have examined factors impacting the achievement of MCID for patient-reported outcomes in similar cohorts, few studies have assessed predictors of early functional improvement.

Methods.

We retrospectively reviewed patients undergoing elective one-level posterior lumbar fusion for degenerative pathology. Patients were subdivided into two groups based on achievement of MCID for each respective PROMIS domain either before six months (“early responders”) or after six months (“late responders”) following surgical intervention. Multivariable logistic regression analysis was used to determine features associated with odds of achieving distribution-based MCID before or after six months follow up.

Results.

147 patients were included. The average age was 64.3±13.0 years. At final follow-up, 57.1% of patients attained MCID for PI and 72.8% for PF. However, 42 patients (49.4%) reached MCID for PI by six months, compared to 44 patients (41.1%) for PF. Patients with severe symptoms had the highest probability of attaining MCID for PI (OR 10.3; P=0.001) and PF (OR 10.4; P=0.001) Preoperative PROMIS symptomology did not predict early achievement of MCID for PI or PF. Patients who received concomitant iliac crest autograft during their lumbar fusion had increased odds of achieving MCID for PI (OR 8.56; P=0.001) before six months.

Conclusion.

Our study demonstrated that the majority of patients achieved MCID following elective one-level lumbar spine fusion at long-term follow-up, although less than half achieved this clinical benchmark for each PROMIS metric by six months. We also found that preoperative impairment was not associated with when patients would achieve MCID. Further prospective investigations are warranted to characterize the trajectory of clinical improvement and identify the risk factors associated with poor outcomes more accurately.
Incidence and Recurrence of Deep Spine Surgical Site Infections
Authors: Freire-Archer Millaray , Sarraj Mohamed , Koziarz Alex , Thornley Patrick , Alshaalan Fawaz , Alnemari Haitham , Kachur Edward , Bhandari Mohit , Oitment Colby
Published: May 2023

Study Design.

Systematic review and meta-analysis.

Objective.

To determine a pooled incidence rate for deep surgical site infection (SSI) and compare available evidence for deep SSI management among instrumented spinal fusions.

Summary of Background Data.

Deep SSI is a common complication of instrumented spinal surgery associated with patient morbidity, poorer long-term outcomes, and higher health care costs.

Materials and Methods.

We systematically searched Medline and Embase and included studies with an adult patient population undergoing posterior instrumented spinal fusion of the thoracic, lumbar, or sacral spine, with a reported outcome of deep SSI. The primary outcome was the incidence of deep SSI. Secondary outcomes included persistent deep SSI after initial debridement, mean number of debridements, and microbiology. The subsequent meta-analysis combined outcomes for surgical site infection using a random-effects model and quantified heterogeneity using the χ2 test and the I
2 statistic. In addition, a qualitative analysis of management strategies was reported.

Results.

Of 9087 potentially eligible studies, we included 54 studies (37 comparative and 17 noncomparative). The pooled SSI incidence rate was 1.5% (95% CI, 1.1%–1.9%) based on 209,347 index procedures. Up to 25% of patients (95% CI, 16.8%–35.3%), had a persistent infection. These patients require an average of 1.4 (range: 0.8–1.9) additional debridements. Infecting organisms were commonly gram-positive, and among them, staphylococcus aureus was the most frequent (46%). Qualitative analysis suggests implant retention, especially for early deep SSI management. Evidence was limited for other management strategies.

Conclusions.

The pooled incidence rate of deep SSI post-thoracolumbar spinal surgery is 1.5%. The rate of recurrence and repeat debridement is at least 12%, up to 25%. Persistent infection is a significant risk, highlighting the need for standardized treatment protocols. Our review further demonstrates heterogeneity in management strategies. Large-scale prospective studies are needed to develop better evidence around deep SSI incidence and management in the instrumented thoracolumbar adult spinal fusion population.
Role of Influenza Vaccination in Cardiovascular Disease: Systematic Review and Meta-Analysis
Authors: Gupta Rahul , Quy Ray , Lin Muling , Mahajan Pranav , Malik Aaqib , Sood Aayushi , Sreenivasan Jayakumar , Bandyopadhyay Dhrubajyoti , Goel Akshay , Agrawal Ankit , Vyas Apurva V. , Patel Nainesh C. , Frishman William H. , Aronow Wilbert S.
Published: May 2023

Influenza vaccination has shown great promise in terms of its cardioprotective effects. The aim of our analysis is to provide evidence regarding the protective effects of influenza vaccination in patients with cardiovascular disease. We conducted a systematic literature search to identify trials assessing the cardiovascular outcomes of influenza vaccination. Summary effects were calculated using a DerSimonian and Laird fixed effects and random effects model as odds ratio with 95% confidence intervals (CIs) for all the clinical endpoints. Fifteen studies with a total of 745,001 patients were included in our analysis. There was lower rates of all-cause mortality [odds ratio (OR) = 0.74, 95% CI 0.64–0.86], cardiovascular death (OR = 0.73, 95% CI 0.59–0.92), and stroke (OR = 0.71, 95% CI 0.57–0.89) in patients who received the influenza vaccine compared to placebo. There was no significant statistical difference in rates of myocardial infarction (OR = 0.91, 95% CI 0.69–1.21) or heart failure hospitalizations (OR = 1.06, 95% CI 0.85–1.31) in the 2 cohorts. In patients with cardiovascular disease, influenza vaccination is associated with lower all-cause mortality, cardiovascular death, and stroke.
Teplizumab Therapy to Delay the Onset of Type 1 Diabetes
Authors: Novograd Joel , Frishman William H.
Published: May 2023

Type 1 diabetes mellitus (T1DM) is an autoimmune disease that results in the destruction of insulin-producing pancreatic beta cells. The incidence and prevalence of T1DM are increasing, making this one of the most common diseases of childhood. The disease is associated with significant morbidity and mortality with patients experiencing reduced quality of life and decreased life expectancy compared with the general population. Patients become dependent on exogenous insulin which has been the primary treatment since its first clinical use over 100 years ago. Although there have been advancements in glucose monitoring technology and insulin delivery devices, most patients fail to meet glycemic targets. Research has therefore focused on different treatment options to delay or prevent disease progression. Monoclonal antibodies have previously been utilized to suppress the immune response following an organ transplant and were subsequently studied for their ability to treat autoimmune diseases. Teplizumab, a monoclonal antibody (manufactured by Provention Bio and marketed as Tzield), was recently approved by the Food and Drug Administration as the first preventative treatment for T1DM. The approval came after a 3-decade history of research and development. This article provides an overview of the discovery and mechanism of action of teplizumab, as well as the clinical trials that led to its approval.
Tropifexor plus cenicriviroc combination versus monotherapy in nonalcoholic steatohepatitis: Results from the phase 2b TANDEM study
Authors: Anstee Quentin M. , Lucas Kathryn J. , Francque Sven , Abdelmalek Manal F. , Sanyal Arun J. , Ratziu Vlad , Gadano Adrian C. , Rinella Mary , Charlton Michael , Loomba Rohit , Mena Edward , Schattenberg Jörn M. , Noureddin Mazen , Lazas Donald , Goh George B.B. , Sarin Shiv K. , Yilmaz Yusuf , Martic Miljen , Stringer Rowan , Kochuparampil Jossy , Chen Li , Rodriguez-Araujo Gerardo , Chng Elaine , Naoumov Nikolai V. , Brass Clifford , Pedrosa Marcos C.
Published: May 2023

Background and Aims:

With distinct mechanisms of action, the combination of tropifexor (TXR) and cenicriviroc (CVC) may provide an effective treatment for NASH. This randomized, multicenter, double-blind, phase 2b study assessed the safety and efficacy of TXR and CVC combination, compared with respective monotherapies.

Approach and Results:

Patients (N = 193) were randomized 1:1:1:1 to once-daily TXR 140 μg (TXR140), CVC 150 mg (CVC), TXR 140 μg + CVC 150 mg (TXR140 + CVC), or TXR 90 μg + CVC 150 mg (TXR90 + CVC) for 48 weeks. The primary and secondary end points were safety and histological improvement, respectively. Rates of adverse events (AEs) were similar across treatment groups. Pruritus was the most frequently experienced AE, with highest incidence in the TXR140 group (40.0%). In TXR and combination groups, alanine aminotransferase (ALT) decreased from baseline to 48 weeks (geometric mean change: −21%, TXR140; −16%, TXR140 + CVC; −13%, TXR90 + CVC; and +17%, CVC). Reductions in body weight observed at week 24 (mean changes from baseline: TXR140, −2.5 kg; TXR140 + CVC, −1.7 kg; TXR90 + CVC, −1.0 kg; and CVC, −0.1 kg) were sustained to week 48. At least 1-point improvement in fibrosis stage/steatohepatitis resolution without worsening of fibrosis was observed in 32.3%/25.8%, 31.6%/15.8%, 29.7%/13.5%, and 32.5%/22.5% of patients in the TXR140, CVC, TXR140 + CVC, and TXR90 + CVC groups, respectively.

Conclusions:

The safety profile of TXR + CVC combination was similar to respective monotherapies, with no new signals. TXR monotherapy showed sustained ALT and body weight decreases. No substantial incremental efficacy was observed with TXR + CVC combination on ALT, body weight, or in histological end points compared with monotherapy.
The puzzle of extensive tinea incognito with a young woman: a case report a tinea incognito with Cushing’s disease
Authors: Xiao Yu , Peng Shanshan , Lin Jie , Hu Youhong , Ye Wenzheng
Published: May 2023

Introduction:

Tinea incognito is a rare condition commonly found in abused topical or systemic steroids. Considering their immunosuppression status, Cushing’s syndrome predisposes patients to infectious diseases. Most patients of Cushing’s syndrome are as a result of adrenocorticotropic hormone production from a pituitary adenoma, which is referred to as Cushing’s disease.

Here, we reported a rare co-occurrence of tinea incognito and Cushing’s syndrome secondary to a giant pituitary tumor.

Case presentation:

Extensive cutaneous and nail lesions were diagnosed with the tinea incognito and tinea unguium, and endocrine or rheumatic disorders were considered as underlying disease-causing extensive tinea incognito. A series of laboratory and imaging tests were performed. We found that a giant pituitary tumor was the primary etiology of multiple cutaneous appearances and secondary disorders. There was an exceptionally unusual co-occurrence of extensive tinea incognito and pituitary adenoma in our case.

Discussion:

We observed a rare co-occurrence of extensive tinea incognito and pituitary adenoma, which should be taken into consideration in the urgent diagnostic criterion of tinea incognito given the potential underlying condition.

Conclusion:

Tinea incognito is not only associated with a history of topical or systemic steroid use, but also the association that underlying diseases related to excessive endogenous steroid production are supported to be taken into account.
Organ preservation strategies after neoadjuvant chemoimmunotherapy in resectable non-small cell lung cancer: a multicenter retrospective cohort study
Authors: Hui Bengang , Wang Xun , Wang Xin , Qiao Bowei , Duan Jiangnan , Shang Rongxin , Yang Weibo , Wang Jun , Chen Kezhong , Yang Fan , Jiang Tao , Lei Jie
Published: May 2023

Background:

Neoadjuvant chemoimmunotherapy has shown a good therapeutic effect on non-small cell lung cancer (NSCLC), which also opens up the possibility of applying organ preservation strategies. This study investigated the feasibility of modified surgery after potent neoadjuvant chemoimmunotherapy in central type NSCLC.

Methods:

In this multicenter retrospective cohort study, patients with central type NSCLC who received 2–4 cycles of neoadjuvant chemoimmunotherapy between January 2019 and June 2022 at Air Force Medical University Tangdu Hospital and Peking University People's Hospital were eligible. Patients were divided into modified and nonmodified groups according to the extent of surgery, after which, the safety and long-term prognosis of surgery were investigated.

Results:

A total of 84 patients were enrolled. Of 36 (42.9%) patients who underwent modified surgery, 21 patients underwent lobectomy, 12 patients underwent lobectomy with bronchoplasty, 2 patients underwent sleeve lobectomy, and 1 patient underwent bilobectomy. The modification rate for the initially estimated pneumonectomy, sleeve lobectomy, and bilobectomy was 48.6, 44.8, and 30%, respectively. Grades II–V postoperative complications were found in 5 (13.9%) patients in the modified group and 17 (35.4%) patients in the nonmodified group (relative risk, 0.393; 95% CI, 0.016–0.963; P=0.026). No significant difference was observed regarding the surgical approach, operative duration, blood loss, or R0 resection rate. The 2-year local recurrence rate was 3.7% (95% CI, 0.004–0.175) and 5.2% (95% CI, 0.012–0.168) in the modified group and nonmodified group, respectively. The 1-year PFS rate of modified and nonmodified groups was 97.1% (95% CI, 83.7–99.8) and 86.9% (95% CI, 73.4–94.4), respectively, while 2-year PFS were 89.8% (95% CI, 74.1–96.9) and 71.8% (95% CI, 56.7–83.4), respectively.

Conclusion:

Applying organ preservation strategies, that is, undergoing modified surgery after neoadjuvant chemoimmunotherapy, is feasible for selected central type NSCLC patients with favorable safety and long-term survival.
Drugs in Focus: Domperidone
Authors: Puoti Maria Giovanna , Assa Amit , Benninga Marc , Broekaert Ilse Julia , Carpi Francisco Javier Martin , Deganello Saccomani Marco , Dolinsek Jernej , Homan Matjaz , Mas Emmanuel , Miele Erasmo , Tzivinikos Christos , Thomson Mike , Borrelli Osvaldo
Published: May 2023

Domperidone is a peripheral dopamine-2 receptor antagonist with prokinetic and antiemetic properties. Its prokinetic effects are mainly manifest in the upper gastrointestinal (GI) tract. Currently its use is restricted to relief of nausea and vomiting in children older than 12 years for a short period of time. However, among (pediatric) gastroenterologists, domperidone is also used outside its authorized indication (“off label”) for treatment of symptoms associated with gastro-esophageal reflux disease, dyspepsia, and gastroparesis. Little is known about its efficacy in the treatment of GI motility disorders in children and controversial data have emerged in the pediatric literature. As its use is off label, appropriate knowledge of its efficacy is helpful to support an “off label/on evidence” prescription. Based on this, the purpose of this review is to summarize all evidence on the efficacy of domperidone for the treatment of GI disorders in infants and children and to report an overview of its pharmacological properties and safety profile.
Nursing Roles in Cancer Rehabilitation
Authors: Justesen Rikke M. , Ikander Tine M. , Thomsen Thora G. , Dieperink Karin B.
Published: May 2023

Background

Because of cancer survivors’ increased need for help and support, cancer rehabilitation should be an essential part of cancer treatment, where focusing on patients’ individual needs is essential.

Objective

To provide an overview of existing evidence about nurses’ roles and participation in cancer rehabilitation, based on both nurses’ and patients’ perspectives.

Methods

A systematic search was conducted in PubMed, CINAHL, EMBASE and Cochrane databases for studies published from January 2001–January 2022. Whittemore and Knafl’s methodology for data extraction and synthesis was used, and PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guidelines were followed. The review was registered in PROSPERO (CRD42021223683).

Results

Ten qualitative studies and 7 quantitative studies were included, encompassing 306 patients and 1847 clinicians (1164 nurses). Three nursing roles emerged: (1) relationship-forming, in which nurses described ongoing involvement in patients’ rehabilitation and patients described nurses as trusted partners; (2) coordinating, in which nurses described a lack of time and resources and a focus on medical treatment, and patients described nurses as expert coordinators; and (3) follow-up, in which patients described nurses as good communicators and trusted partners in their follow-up, and nurses described their natural interest in patients’ rehabilitation outcomes during follow-up.

Conclusions

Patients were comfortable with nurses as trusted partners during cancer rehabilitation. Significant barriers such as lack of time, resources, and education about rehabilitation may negatively influence rehabilitation planning, implementation, and monitoring.

Implications for Practice

Clinicians can use the findings to improve cancer rehabilitation with the nurse as a central provider and conduct further research on the coordinating and follow-up roles.