bluuebunny/crossref_metadata_2025 huggingface dataset:
A report of Rosai–Dorfman disease with systemic multiple lymphadenopathy and high IgG4 plasma cell infiltration
Authors: Liu Pingdan , Lv Pan , Zhu Maoling , Liu Jianping
Published: April 2023

The Rosai-Dorfman disease (RDD) is a kind of sinus histiocytosis with massive lymphadenopathy and is remarkably rare. RDD is characterized by large histiocytes with emperipolesis. However, the cause of RDD is unknown, and most cases are relieved spontaneously. In rare cases, patients may have onset and remission of lymph nodes and extranodal involvement. This report showed an RDD case in a 67-year-old male patient with systemic superficial lymphadenopathy and high IgG4 plasma cell infiltration. We showed that a possible RDD diagnosis should be kept in mind when encountering a systemic multiple lymphadenopathy and high IgG4 plasma cell infiltration. Also, an overlap between RDD and IgG4-related disease might be present, which might help in clinical recognition of RDD.
Thinking generically and specifically in International Relations survey experiments
Authors: Suong Clara H , Desposato Scott , Gartzke Erik
Published: April 2023

Does treatment abstraction affect treatment effects in International Relations survey experiments in countries outside of the US? We assess whether treatment effects are conditional on the anonymity of country actors among respondents in Brazil, China, Sweden, Japan, and Ukraine. We examine whether the effects of the United Nations’ approval of military force and regime type of the target country on support for war are moderated by respondents’ compliance with our abstraction encouragement. We find that around 20% of the respondents across all samples think of specific countries and do not comply with our abstraction encouragement. However, we fail to find evidence of a change in the average treatment effects by non-compliance, implying that the treatment effects are not likely to be conditional on respondents’ compliance (thinking of specific cases) or schema inconsistency (thinking of specific cases that are implausible given the context). At the same time, we find that treatment inconsistency (thinking of specific cases that are inconsistent with the assigned treatments) can affect the main treatment effects.
Trabecular Bone Remodeling After Posterior Lumbar Interbody Fusion: Comparison of Three-Dimensional Porous Tantalum and Titanium-Coated Polyetheretherketone Interbody Cages
Authors: Segi Naoki , Nakashima Hiroaki , Shinjo Ryuichi , Kagami Yujiro , Machino Masaaki , Ito Sadayuki , Ouchida Jun , Morishita Kazuaki , Oishi Ryotaro , Yamauchi Ippei , Imagama Shiro
Published: April 2023

Study Design

Retrospective cohort study

Objectives

The criteria for determining completion of intervertebral stability after posterior lumbar interbody fusion (PLIF) remain controversial. Several new radiological indicators of bone growth and osteointegration have been established. We compared computed tomography (CT) findings related to osteointegration after PLIF with interbody cages of two different materials and designs.

Methods

We retrospectively analyzed data from 103 patients who underwent PLIF with three-dimensional porous tantalum (Tn) cages or titanium-coated polyetheretherketone (TiP) cages. CT images obtained 3 months and 1 year after surgery were examined for trabecular bone remodeling (TBR), cancellous condensation (CC), and vertebral endplate cyst (VEC) formation. The incidences of each finding were compared by cage type, and rates of instrument failure and pseudarthrosis were determined.

Results

Three months postoperatively, 87% of the levels with Tn cages exhibited TBR, whereas 96% of those with TiP cages did not (P < .001). Most levels with Tn cages levels exhibited TBR and no CC 3 months (81%) and 1 year (94%) after surgery. Although 78% of levels with TiP cages exhibited CC and no TBR 3 months after surgery, 59% exhibited both CC and TBR 1 year after surgery. Significantly fewer VECs formed around the Tn cages than around the TiP cages both 3 months (P = .002) and 1 year (P < .001) after surgery. Implant-related problems occurred at levels that exhibited neither TBR nor CC.

Conclusions

The porous tantalum cage may enable intervertebral stability that is comparable to bony fusion soon after surgery.
Influence of R&D and ICT Capabilities on Innovation Performance: Evidence from Indian Firms
Authors: Nag Tirthankar , Ganguly Boudhayan , Singh Rohit , Shrivastava Avinash K.
Published: April 2023

Innovation plays a critical role in the growth of developing economies like India. The primary purpose of the current study is to investigate the role of research and development (R&D) and Information and communication technology (ICT) in firms’ innovation outcomes. The study uses data from firm-level surveys in India to examine the linkages of R&D and ICT on innovation outcomes and establishes linkages with policy elements to develop innovation ecosystems. The study uses a set of tobit regression models, generalized structural equations model and explorative content analysis to examine innovation outcomes of firms. The results indicate that both R&D and ICT parameters play a significant role in influencing innovation outcomes though they are moderated by the size of the firm and sector. The study adds to the existing literature on the resource-based view of the firm and also the literature on innovation management in the context of emerging economies. The authors examine the role of capabilities around R&D and ICT in influencing firm-level innovations.
Work-Stress Content Analysis Using Social Media Data
Authors: Agarwal Reeti , Mehrotra Ankit
Published: April 2023

Since its occurrence in December 2019, COVID-19 has adversely affected both the personal and professional lives of people across the world. The widespread continuance of the pandemic has increased feelings of stress among people. Focusing on content analysis of data collected from Twitter, a social media platform, the current article aims at identifying and analyzing job-related stress among the masses with a focus on two primary terms related to stress among working people—employment and unemployment. A total of 32,237 tweets were downloaded from locations of four major cities of India, namely, Delhi, Mumbai, Kolkata and Chennai based on the keywords used for the study. Content analysis using R was employed as the technique to study the correlation and association of terms to find linkages between feelings/sentiments shared by the masses. Two clusters (Speculative and Misfit-Originators) of job-related stress causes were identified and coping strategies were suggested based on the reasons for stress in the different clusters. The findings suggest that increasing the perception of volition and allaying fears act as coping strategies for employees.
Mosunetuzumab monotherapy is active and tolerable in patients with relapsed/refractory diffuse large B-cell lymphoma
Authors: Bartlett Nancy L. , Assouline Sarit , Giri Pratyush , Schuster Stephen J. , Cheah Chan Y. , Matasar Matthew , Gregory Gareth P. , Yoon Dok Hyun , Shadman Mazyar , Fay Keith , Yoon Sung-Soo , Panizo Carlos , Flinn Ian , Johnston Anna , Bosch Francesc , Sehn Laurie H. , Wei Michael C. , Yin Shen , To Iris , Li Chi-Chung , Huang Huang , Kwan Antonia , Penuel Elicia , Budde Lihua E.
Published: April 2023

As part of a phase 1 or 2 study, this single-arm expansion cohort established the efficacy and safety of mosunetuzumab monotherapy in patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) (received ≥2 previous lines of therapy). Intravenous mosunetuzumab was administered with cycle (C) 1 step-up dosing for cytokine release syndrome (CRS) mitigation: C1 day (D) 1: 1 mg; C1D8 2 mg; C1D15 and C2D1: 60 mg; C3 + D1: 30 mg. Hospitalization was not mandatory. Patients with complete response (CR) completed treatment after C8; those with partial response or stable disease continued treatment for a total of 17 cycles. The primary end point was CR rate (best response), assessed against a historical control CR rate (20%) by independent review facility. Eighty-eight patients (73.9% de novo DLBCL; 26.1% transformed follicular lymphoma) were enrolled; all had received previous anthracycline and anti-CD20 therapy. Overall response and CR rates were 42.0% (95% confidence interval [CI], 31.6-53.1) and 23.9% (95% CI, 15.4-34.1), respectively; CR rate did not reach statistical significance vs the historical control (P = .36). Median time to first response was 1.4 months. Median progression-free survival was 3.2 months (95% CI, 2.2-5.3). The CR rate in 26 patients who received previous chimeric antigen receptor T-cell (CAR-T) therapy was 12%. CRS was one of the most common adverse events (26.1% of patients); predominantly grade 1 to 2 and primarily in C1. Four patients (4.5%) discontinued mosunetuzumab owing to adverse events. Mosunetuzumab demonstrated notable efficacy and a manageable safety profile in patients with R/R DLBCL, including those previously treated with CAR-Ts. This trial was registered at www.clinicaltrials.gov as #NCT02500407.
Chromatin accessibility differences between alpha, beta, and delta cells identifies common and cell type-specific enhancers
Authors: Mawla Alex M. , van der Meulen Talitha , Huising Mark O.
Published: April 2023

Background

High throughput sequencing has enabled the interrogation of the transcriptomic landscape of glucagon-secreting alpha cells, insulin-secreting beta cells, and somatostatin-secreting delta cells. These approaches have furthered our understanding of expression patterns that define healthy or diseased islet cell types and helped explicate some of the intricacies between major islet cell crosstalk and glucose regulation. All three endocrine cell types derive from a common pancreatic progenitor, yet alpha and beta cells have partially opposing functions, and delta cells modulate and control insulin and glucagon release. While gene expression signatures that define and maintain cellular identity have been widely explored, the underlying epigenetic components are incompletely characterized and understood. However, chromatin accessibility and remodeling is a dynamic attribute that plays a critical role to determine and maintain cellular identity.

Results

Here, we compare and contrast the chromatin landscape between mouse alpha, beta, and delta cells using ATAC-Seq to evaluate the significant differences in chromatin accessibility. The similarities and differences in chromatin accessibility between these related islet endocrine cells help define their fate in support of their distinct functional roles. We identify patterns that suggest that both alpha and delta cells are poised, but repressed, from becoming beta-like. We also identify patterns in differentially enriched chromatin that have transcription factor motifs preferentially associated with different regions of the genome. Finally, we not only confirm and visualize previously discovered common endocrine- and cell specific- enhancer regions across differentially enriched chromatin, but identify novel regions as well. We compiled our chromatin accessibility data in a freely accessible database of common endocrine- and cell specific-enhancer regions that can be navigated with minimal bioinformatics expertise.

Conclusions

Both alpha and delta cells appear poised, but repressed, from becoming beta cells in murine pancreatic islets. These data broadly support earlier findings on the plasticity in identity of non-beta cells under certain circumstances. Furthermore, differential chromatin accessibility shows preferentially enriched distal-intergenic regions in beta cells, when compared to either alpha or delta cells.
Assessment of the nasal microbiota in dogs with fungal rhinitis before and after cure and in dogs with chronic idiopathic rhinitis
Authors: Vangrinsven Emilie , Fastrès Aline , Taminiau Bernard , Billen Frédéric , Daube Georges , Clercx Cécile
Published: April 2023

Background

Pathogenesis of canine fungal rhinitis is still not fully understood. Treatment remains challenging, after cure turbinate destruction may be associated with persistent clinical signs and recurrence of fungal rhinitis can occur. Alterations of the nasal microbiota have been demonstrated in dogs with chronic idiopathic rhinitis and nasal neoplasia, although whether they play a role in the pathogenesis or are a consequence of the disease is still unknown. The objectives of the present study were (1) to describe nasal microbiota alterations associated with fungal rhinitis in dogs, compared with chronic idiopathic rhinitis and controls, (2) to characterize the nasal microbiota modifications associated with successful treatment of fungal rhinitis. Forty dogs diagnosed with fungal rhinitis, 14 dogs with chronic idiopathic rhinitis and 29 healthy control dogs were included. Nine of the fungal rhinitis dogs were resampled after successful treatment with enilconazole infusion.

Results

Only disease status contributed significantly to the variability of the microbiota. The relative abundance of the genus Moraxella was decreased in the fungal rhinitis (5.4 ± 18%) and chronic idiopathic rhinitis (4.6 ± 8.7%) groups compared to controls (51.8 ± 39.7%). Fungal rhinitis and chronic idiopathic rhinitis groups also showed an increased richness and α-diversity at species level compared with controls. Increase in unique families were associated with fungal rhinitis (Staphyloccaceae, Porphyromonadaceae, Enterobacteriaceae and Neisseriaceae) and chronic idiopathic rhinitis (Pasteurellaceae and Lactobacillaceae). In dogs with fungal rhinitis at cure, only 1 dog recovered a high relative abundance of Moraxellaceae.

Conclusions

Results confirm major alterations of the nasal microbiota in dogs affected with fungal rhinitis and chronic idiopathic rhinitis, consisting mainly in a decrease of Moraxella. Besides, a specific dysbiotic profile further differentiated fungal rhinitis from chronic idiopathic rhinitis. In dogs with fungal rhinitis, whether the NM returns to its pre-infection state or progresses toward chronic idiopathic rhinitis or fungal rhinitis recurrence warrants further investigation.
Antioxidant effects of Bifidobacterium longum T37a in mice weight loss and aging model induced by D-galactose
Authors: Wang Ya , Wang Jiahui , Li Hehai , Lao Jianlong , Jia Dan , Liu Junlong , Wang Jinming , Luo Jianxun , Guan Guiquan , Yin Hong , Li Youquan
Published: April 2023

Background

Probiotics can reduce free radical scavenging rate and oxidative damage, and improve activity of crucial antioxidative enzymes in host cells. This study aimed to isolate Bifidobacterium spp. from faeces of babies, and investigate the antioxidant effects of the Bif. longum T37a in mice weight loss and aging model induced by D-galactose.

Results

T37a have good antioxidant properties in the DPPH assay and anti-lipid peroxidation test. Compared with the model group, T37a low group significantly increased the thymus index and the levels of T-AOC and GSH-Px of mice. T37a high group significantly decreased the spleen and liver index of mice and the levels of MDA in liver, significantly increased in liver HDL-C levels, and decreased LDL-C in liver.

Conclusions

T37a may be an anti-aging and weight-loss probiotics for its antioxidant capacity, and it is necessary to study further the molecular mechanism of T37a as antioxidant.
A new method to separate the impacts of interday and intraday temperature variability on mortality
Authors: Wen Bo , Wu Yao , Guo Yuming , Li Shanshan
Published: April 2023

Background

Temperature variability (TV) is associated with increased mortality risks. However, the independent impacts of interday and intraday are still unknown.

Methods

We proposed a new method to decompose TV into interday TV and intraday TV through algebra derivation. Intraday TV was defined as the weighted average standard deviation (SD) of minimum temperature and maximum temperature on each day. Interday TV was defined as the weighted SD of daily mean temperatures during the exposure period. We then performed an illustrative analysis using data on daily mortality and temperature in France in 2019–2021.

Results

The novel interday and intraday TV indices were good proxies for existing indicators, inlcluding diurnal temperature range (DTR) and temperature change between neighbouring days (TCN). In the illustrative analyses, interday and intraday TVs showed differentiated mortality risks. Mortality burden related to TV was mainly explained by the intraday component, accounting for an attributable fraction (AF) of 1.81% (95% CI: 0.64%, 2.97%) of total mortality, more than twice the AF of interday TV (0.86%, 95% CI: 0.47%, 1.24%).

Conclusions

This study proposed a novel method for identifying and isolating the different components of temperature variability and offered a comprehensive way to investigate their health impacts.
Randomized prospective trial to detect and distinguish between medication nonadherence, drug-drug interactions, and disease progression in chronic cardiometabolic disease
Authors: Peabody John W , Ganesan Divya , Valdenor Czarlota , Paculdo David , Schrecker Joshua , Westerfield Christopher , Heltsley Rebecca
Published: April 2023

Background

Disentangling nonadherence (NA), drug-drug interactions (DDIs), and disease progression from each other is an important clinical challenge for providers caring for patients with cardiometabolic diseases. NAs and DDIs are both ubiquitous and often overlooked. We studied a novel chronic disease management (CDM) test to detect medication adherence and the presence and severity of DDIs.

Materials and methods

We conducted a prospective, randomized controlled trial of 236 primary care physicians using computer-based, simulated patients, measuring clinical care with and without access to the CDM test. The primary outcomes were whether use of the CDM test increased the accuracy of diagnoses and ordering better treatments and how effective the intervention materials were in getting participants to order the CDM test.

Results

Physicians given the CDM test results showed a + 13.2% improvement in their diagnosis and treatment quality-of-care scores (p < 0.001) in the NA patient cases and a + 13.6% improvement in the DDI cases (p < 0.001). The difference-in-difference calculations between the intervention and control groups were + 10.4% for NA and + 10.8% for DDI (p < 0.01 for both). After controlling for physician and practice co-factors, intervention, compared to control, was 50.4x more likely to recognize medication NA and 3.3x more likely to correctly treat it. Intervention was 26.9x more likely to identify the DDI and 15.7x more likely to stop/switch the interacting medication compared to control. We found no significant improvements for the disease progression patient cases.

Conclusion

Distinguishing between nonadherence, drug-drug interactions, and disease progression is greatly improved using a reliable test, like the CDM test; improved diagnostic accuracy and treatment has the potential to improve patient quality of life, medication safety, clinical outcomes, and efficiency of health delivery.

Trial Registration

clinicaltrials.gov (NCT05192590).
Characteristics and outcomes of COVID-19 patients during the BA.5 omicron wave in Tehran, Iran: a prospective observational study
Authors: Salehi Mohammadreza , Salami Khaneshan Arezoo , Farahani Abbas Shakoori , Doomanlou Mahsa , Arabzadeh Mohammad , Sobati Abolfazl , Farhadi Kousha , Fattahi Reza , Mohammadnejad Esmaeil , Abdoli Asghar , Zebardast Jayran
Published: April 2023

Background

Omicron (B.1.1.529) is the fifth variant of concern of SARS-CoV-2, which has several subvariants. Clinical features of BA.1 and BA.2 infections have been described in the literature, but we have limited information about the clinical profile of BA.5, which caused the seventh wave in Iran.

Methods

A prospective observational study was conducted on the BA.5 confirmed patients referred to Imam Khomeini Hospital Complex, Tehran, Iran, from 11th to 31st August 2022. The patients were divided into the two groups of outpatients and hospitalized patients, and their clinical, radiological, and laboratory data and outcomes were recorded and analyzed.

Results

We included 193 patients with confirmed BA.5 infection, of whom 48 patients (24·8%) were hospitalized. The mean age of the patients was 45·3 ± 16·5 years, and 113 patients (58·5%) were female. The mean number of days patients had symptoms was 6·8 ± 2·4 days. The most common symptoms were weakness (69·9%), sore throat (67·4%), myalgia (66·3%), hoarseness (63·7%), headache (55·4%), fatigue (54·9%), and dry cough (50·3%). Fever and dyspnea were significantly more observed in the hospitalized patients (p < 0·0001). The COVID-19 vaccination rate was significantly lower in hospitalized patients than in outpatients (35/48–72·9% vs. 140/145 − 96·6%, p < 0·0001). The most common underlying diseases were hypertension (16·1%), diabetes mellitus (9·8%), and cardiovascular diseases (9·8%), all of which were significantly more common in hospitalized patients. Lung opacities were observed in 81·2% of hospitalized patients. By the end of our study, 1·5% of patients died despite receiving critical care services.

Conclusions

Our findings suggested that BA.5 symptoms are more non-respiratory and usually improve within 7 days. Although the proportion of hospitalized patients is still significant, very few patients require intensive care. COVID-19 vaccination is effective in reducing the hospitalization rate.

Trial registration

Not applicable. This study is not a clinical trial.
Providers’ perspectives of the neonatal intensive care unit context and care provision for adolescent parents: an interpretive description
Authors: Orr Elizabeth , Ballantyne Marilyn , Gonzalez Andrea , Jack Susan Michelle
Published: April 2023

Background

The neonatal intensive care unit (NICU) is a complex care environment, with the NICU patient population among the most vulnerable in a hospital setting. Adolescent parents are a unique group within the broader NICU parent population and admission of their infant to the NICU contributes to an already complex situation as adolescent pregnancy and parenting is often associated with a range of psychosocial challenges. How the NICU care context influences care provision for adolescent parents is a significant gap in the NICU parenting and support discourse. Therefore, this study aimed to explore health and social care providers’ perspectives of the NICU care context and how providers perceive the context as influencing the experiences of adolescent parents in the NICU.

Methods

This was a qualitative, interpretive description study design. In-depth interviews were conducted with providers, including nurses and social workers, caring for adolescent parents in the NICU. Data was collected between December 2019 and November 2020. Data were analyzed concurrently with data collection. Constant comparison, analytic memos, and iterative diagramming techniques were used to challenge developing analytic patterns.

Results

Providers (n = 23) described how the unit context influenced care provision as well as experiences for adolescent parents. We learned that having a baby in the NICU was perceived by providers as a traumatic experience for parents – impacting attachment, parenting confidence and competence, and mental health. Environmental factors – such as privacy and time – and perceptions that adolescent parents are treated differently in the NICU were also seen as influencing this overall experience.

Conclusions

Providers involved in the care of adolescent parents in the neonatal intensive care unit described the distinctiveness of this group within the broader parent population and how quality of care may be impacted by contextual factors as well as experiences of age-related stigma. Further understanding of NICU experiences from the parents’ perspectives are warranted. Findings highlight opportunities for strengthened interprofessional collaboration and trauma- and violence-informed care strategies within the neonatal intensive care environment to mitigate the potential negative influence of this experience and improve care for adolescent parents.
Real-life experiences with CAR T-cell therapy with idecabtagene vicleucel (ide-cel) for triple-class exposed relapsed/refractory multiple myeloma patients
Authors: Sanoyan Dilara Akhoundova , Seipel Katja , Bacher Ulrike , Kronig Marie-Noelle , Porret Naomi , Wiedemann Gertrud , Daskalakis Michael , Pabst Thomas
Published: April 2023

Background

Chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment landscape of relapsed/refractory multiple myeloma (RRMM), leading to unprecedented responses in this patient population. Idecabtagene vicleucel (ide-cel) has been recently approved for treatment of triple-class exposed RRMM. We report real-life experiences with the commercial use of ide-cel in RRMM patients.

Methods

We performed a retrospective analysis of the first 16 triple-class exposed RRMM patients treated with ide-cel at a single academic center. We assessed toxicities, response to treatment, CAR T expansion and soluble BCMA (sBCMA) levels.

Results

We identified 16 consecutive RRMM patients treated with ide-cel between 06–10/2022. Median age was 69 years, 6 (38%) patients had high-risk cytogenetics, 3 (19%) R-ISS stage III, and 5 (31%) extramedullary disease. Median number of previous treatment lines was 6 (3–12). Manufacturing success rate was 88% (6% required second lymphapheresis, 6% received an out-of-specification product). At 3 months, the overall response rate (ORR) was 69% (44% sCR, 6% CR, 19% VGPR). Cytokine release syndrome (CRS) occurred in 15 (94%) patients (88% G1, 6% G2), immune effector-cell associated neurotoxicity syndrome (ICANS) in 1 (6% G1), febrile neutropenia in 11 (69%), and infections in 5 (31%). Prolonged hematologic toxicity occurred in 4/16 (25%) patients. Other non-hematological toxicities were elevated hepatic enzymes (38%), colitis (6%, G3) and DIC (6%, G2). Responses were more frequent in patients with higher CAR T expansion (100% vs 38%), and lack of decrease or plateau of sBCMA levels was typically observed in non-responders.

Conclusions

We report one of the first cohorts of RRMM treated with commercial ide-cel. The ORR was 69% and safety profile was manageable, but prolonged hematologic toxicity still represents a major challenge. Responses correlated with in vivo CAR T cell expansion, underlining the need of further research to optimize CAR T expansion.
The effect of gabapentin and pregabalin administration on memory in clinical and preclinical studies: a meta-analysis and systematic review
Authors: Behroozi Zahra , Jafarpour Maral , Razmgir Maryam , Saffarpour Sepideh , Azizi Hanieh , Kheirandish Ali , Kosari-rad Tahereh , Ramezni Fatemeh , Janzadeh Atousa
Published: April 2023

Background

Today, gabapentinoids such as Gabapentin (GBP) and pregabalin (PGB) are widely used as painkillers. This may alter the function of the nervous system; hence their results may include a difference in memory and processes that end in memory formation. This study aims to conclude whether gabapentinoids can alter memory or not by reviewing and analyzing clinical and preclinical studies.

Material and methods

A comprehensive search was carried out in databases including PUBMED, EMBASE, SCOPUS, and Web of Science. In the included studies, memory was measured as an outcome variable in clinical or preclinical studies.

Result

A total of 21 articles (4 clinical, 17 preclinical) were included in the meta-analysis by STATA Software. The results showed that memory changes under the influence of GBP. Both the administrated dosage and the time of administration are important in the final results and latency time of retention. GBP administration in healthy animals increased latency time, whereas if the administration of GBP took place exactly before training, the latency time increased slightly.

Short-term administration of PGB in healthy volunteers is accompanied by transient side effects on the CNS. However, the number and homogeneity of the studies were not such that a meta-analysis could be performed on them.

Conclusion

Clinical and preclinical studies showed that PGB administration did not confirm its improving memory effect. GBP administration in healthy animals increased latency time and improved memory. Although it depended on the time of administration.
Rapid resolution of catatonia secondary to post traumatic stress disorder with secondary psychotic features through scheduled zolpidem tartrate
Authors: Bonomo Nicholas , Huang Haojiang , Schoenbachler Ben
Published: April 2023

Catatonia is a complication of numerous psychiatric and medical conditions. The first-line treatment is typically management of the underlying primary condition as well as scheduled benzodiazepines or electroconvulsive therapy. Electroconvulsive therapy and benzodiazepines are not always tolerated or available when treating patients with catatonia. For this reason, other treatment regimens have been trialed in recent years, including the GABA-modulatory Z drugs such as zolpidem. Some alternative treatment modalities have shown great promise. However, which populaces these are most beneficial for is still unclear. In this article, we examine a case report of a woman who suffered from post-traumatic stress disorder with secondary psychotic features who experienced recurrent akinetic catatonia that was refractory to benzodiazepine therapy. She responded rapidly to scheduled zolpidem with minimal side effects. It is our author’s belief that when managing catatonia in patients with post traumatic stress disorder with secondary psychosis, Z drugs may be preferable to benzodiazepines.
5-alpha reductase inhibitors and MRI prostates: actively reducing prostate sizes and ambiguity
Authors: Wang Ziting , Wang Kaiying , Ong Han Yang , Tsang Woon Chau , Wu Qing Hui , Chiong Edmund
Published: April 2023

Background

Magnetic resonance imaging (MRI) scans are increasingly first-line investigations for suspected prostate cancer, and essential in the decision for biopsy. 5-alpha reductase inhibitor (5-ARI) use has been shown to reduce prostate size and prostate cancer risk. However, insufficient data exists on how 5-ARI use affects MRI findings and yield of biopsy. This study explores the differences in imaging and prostate cancer diagnoses between patients receiving and not receiving 5-ARI therapy.

Methods

From 2015 to 2020, we collected retrospective data of consecutive patients undergoing prostate biopsy at one centre. We included patients who were biopsy-naïve, had prior negative biopsies, or on active surveillance for low-grade prostate cancer. Clinical and pathological data was collected, including 5-ARI use, Prostate Imaging Reporting and Data System (PIRADS) classification and biopsy results.

Results

351 men underwent saturation biopsy with or without targeted biopsies. 54 (15.3%) had a history of 5-ARI use. On mpMRI, there was no significant difference between the 5ARI and non-5-ARI groups in PIRADS distribution, number of lesions, and lesion location. Significantly fewer cancers were detected in the 5-ARI group (46.3% vs. 68.0%; p < 0.01). There were no significant differences in PIRADS distribution in 5-ARI patients with positive and negative biopsy.

Conclusion

Our study found significant differences in biochemical, imaging and biopsy characteristics between 5-ARI and non-5-ARI groups. While both groups had similar PIRADS distribution, 5-ARI patients had a lower rate of positive biopsies across all PIRADS categories, which may suggest that the use of 5ARI may confound MRI findings. Further studies on how 5-ARI therapy affects the imaging characteristics of prostate cancer should be performed.
Root and canal morphology of mandibular second molars in an Egyptian subpopulation: a cone-beam computed tomography study
Authors: Saber Shehabeldin Mohamed , Seoud Mohammed abou El , Sadat Shaimaa Mohamed Abu el , Nawar Nawar Naguib
Published: April 2023

Background

This study was using Cone beam computed tomography (CBCT) to examine the anatomical variations in mandibular second molars in an Egyptian sub-population.

Methods

A total of 350 CBCT images (215 females and 135 males, aged 15–65 years) of mandibular second molars were evaluated. Samples were evaluated in terms of: number of roots, number of root canals, roots’ cross section as well as prevalence and configurations of C-shaped canals. Statistical analysis was done to highlight differences between different categories and their prevalence among genders (significance level was set at p < 0.05). Data were presented as frequency and percentage values and were analyzed using chi square test followed by pairwise comparisons utilizing multiple Fisher’s exact tests with Bonferroni correction. The significance level was set at p < 0.05 within all tests.

Results

Of the 350 mandibular second molars evaluated, 87.2% were non-C-shaped while 12.8% were C-shaped with no gender-based statistically significant differences (χ2 = 0.19, p = 0.656). Most samples had three root canals (80%) followed by two (16%), then one (3.2%), and finally four (0.8%) root canals. Among the non-C-shaped molars, presence of two roots was most common (83.4%) followed by presence of a single root (16.2%), and only one sample (0.2%) had three roots, and this had no correlation with gender (χ2 = 1.86, p = 0.431). In the mesial roots Type IV Vertucci was the most common configuration found (68.8%), while Type I was the most prevalent in the distal roots (91.8%). The long oval configuration was the most commonly found cross section in mesial roots while “oval” was the most prevalent in distal roots.

Conclusion

Egyptian sub-population shows highly variable morphological features in mandibular second molars, hence, CBCT is highly recommended on case-to-case conditions.
Methadone rotation versus other opioid rotation for refractory cancer induced bone pain: protocol of an exploratory randomised controlled open-label study
Authors: Michael Natasha , Sulistio Merlina , Wojnar Robert , Gorelik Alexandra
Published: April 2023

Background

A third of patients with advanced cancer and bone metastasis suffer from cancer induced bone pain (CIBP), impeding quality of life, psychological distress, depression and anxiety. This study will evaluate the impact of an opioid rotation, comparing methadone rotation with other opioid rotation in patients with refractory CIBP.

Methods

This open-label randomised controlled trial will recruit cancer patients with CIBP and inadequate pain control despite established baseline opioid and/or intolerable opioid side effects from cancer and palliative care services. Participants will be at least 18 years old, with a predicted prognosis of greater than 8 weeks, meet the core diagnostic criteria for CIBP, have a worst pain score of ≥ 4 of 10 from CIBP and/ or have opioid toxicity (graded ≥ 2 on Common Terminology Criteria for Adverse Events). Participants will have sufficiently proficient English to complete questionnaires and provide informed consent.

Participants will be randomised 1:1 to be rotated to methadone to another opioid. The primary objective is to examine the impact of opioid rotation in improving CIBP by comparing analgesic efficacy, safety and tolerability in the two arms. Secondary objectives will assess changes in the intensity, duration and frequency of breakthrough pain, requirement of breakthrough analgesia, overall opioid escalation index, and time taken to observe improvement in pain reduction, pain interference and quality of life.

Discussion

Laboratory studies suggest the involvement of neuropathic involvement in the mechanism of CIBP, though there remains no clear evidence of the routine use of neuropathic agents. Methadone as an analgesic agent may have a role to play in this cohort of patients, thus warranting further exploratory studies.

Trial Registration

Australian New Zealand Clinical Trials Registry No: ACTRN12621000141842. Registered 11 February 2021.
Translation and cross-cultural adaptation of the National Health Service Sustainability Model to the Chinese healthcare context
Authors: Lai Jie , Maher Lynne , Li Chaixiu , Zhou Chunlan , Alelayan Hasan , Fu Jiaqi , Wu Yanni
Published: April 2023

Background

International attention is being paid to the issue of making evidence sustainable after implementation. Developing an identification model is essential to promote and monitor the sustainability of evidence implementation. However, this model is not available in Chinese. This study aims to translate the National Health Service Sustainability Model into Chinese and to verify whether the model is adapted to the Chinese healthcare environment.

Methods

This study follows the translation and validation guidelines developed by Sousa and Rojjanasrirat. The translations include forward and backward translations and their comparison. Expert reviews were used to validate the content validity of the Chinese version of the National Health Service sustainability model. Cognitive interviews were used to assess the validity of the language in the Chinese setting.

Results

The translation was conducted by a bilingual research team and took 12 months. Expert reviews were undertaken with eight experts, and cognitive interviews with six participants. The content validity of the model is excellent, but at least 20% of the experts still felt that items one, three, five and nine needed refinements. In the cognitive interviews, most items, instructions and response options were well understood by the participants responsible for the evidence-based practice project. However, some language issues were still identified in items one, three, four, five, seven, nine, and ten. Participants reported that the sustainability results of the model assessment were consistent with their previous judgments of the items. Based on the expert review and interview results, items one, three, four, five, seven, nine and ten require further refinement. In summary, seven of the ten items have been amended.

Conclusions

This study provides insight into how the National Health Service sustainability model can be used in the Chinese healthcare setting and paves the way for future large-scale psychometric testing.
Discovery of novel amino acid production traits by evolution of synthetic co-cultures
Authors: Zuchowski Rico , Schito Simone , Neuheuser Friederike , Menke Philipp , Berger Daniel , Hollmann Niels , Gujar Srushti , Sundermeyer Lea , Mack Christina , Wirtz Astrid , Weiergräber Oliver H. , Polen Tino , Bott Michael , Noack Stephan , Baumgart Meike
Published: April 2023

Background

Amino acid production features of Corynebacterium glutamicum were extensively studied in the last two decades. Many metabolic pathways, regulatory and transport principles are known, but purely rational approaches often provide only limited progress in production optimization. We recently generated stable synthetic co-cultures, termed Communities of Niche-optimized Strains (CoNoS), that rely on cross-feeding of amino acids for growth. This setup has the potential to evolve strains with improved production by selection of faster growing communities.

Results

Here we performed adaptive laboratory evolution (ALE) with a CoNoS to identify mutations that are relevant for amino acid production both in mono- and co-cultures. During ALE with the CoNoS composed of strains auxotrophic for either l-leucine or l-arginine, we obtained a 23% growth rate increase. Via whole-genome sequencing and reverse engineering, we identified several mutations involved in amino acid transport that are beneficial for CoNoS growth. The l-leucine auxotrophic strain carried an expression-promoting mutation in the promoter region of brnQ (cg2537), encoding a branched-chain amino acid transporter in combination with mutations in the genes for the Na+/H+-antiporter Mrp1 (cg0326-cg0321). This suggested an unexpected link of Mrp1 to l-leucine transport. The l-arginine auxotrophic partner evolved expression-promoting mutations near the transcriptional start site of the yet uncharacterized operon argTUV (cg1504-02). By mutation studies and ITC, we characterized ArgTUV as the only l-arginine uptake system of C. glutamicum with an affinity of KD = 30 nM. Finally, deletion of argTUV in an l-arginine producer strain resulted in a faster and 24% higher l-arginine production in comparison to the parental strain.

Conclusion

Our work demonstrates the power of the CoNoS-approach for evolution-guided identification of non-obvious production traits, which can also advance amino acid production in monocultures. Further rounds of evolution with import-optimized strains can potentially reveal beneficial mutations also in metabolic pathway enzymes. The approach can easily be extended to all kinds of metabolite cross-feeding pairings of different organisms or different strains of the same organism, thereby enabling the identification of relevant transport systems and other favorable mutations.
Excessive exogenous cholesterol activating intestinal LXRα-ABCA1/G5/G8 signaling pathway can not reverse atherosclerosis in ApoE−/− mice
Authors: Yu Xichao , Ding Xue , Feng Han , Bi Yunhui , Li Yu , Shan Jinjun , Bian Huimin
Published: April 2023

Background

The long-term excessive intake of exogenous cholesterol can lead to abnormally elevated blood lipid levels and induce cardiovascular and cerebrovascular diseases. However, the influence and relevance of exogenous cholesterol on plasma cholesterol components were still unclear, and the influence on intestinal lipid metabolism targets needs to be further explored.

Methods

In vivo, the C57BL/6 + NF group and ApoE−/− + NF group mice were fed a normal specific pathogen-free (SPF) diet; the ApoE−/− + HF group mice were fed a high-cholesterol SPF diet. The plasma and jejunum tissue homogenate were obtained for non-targeted lipid metabolomics. The lipid droplets in tissues were observed by transmission electron microscope and oil red O staining. Jejunum tissue morphology was observed by HE staining. The kits were used to detect lipid content in plasma, tissues, intestinal contents, and cells. Western blot, RT-PCR, immunohistochemistry (IHC), and immunofluorescence (IF) were used to observe the key target of lipid metabolism. In vitro, the final concentration of cholesterol was 100 μmol/L in Caco-cells. Oil red O staining, western blot, RT-PCR and immunofluorescence (IF) were used to observe the changes of lipid metabolism. Finally, the influence of liver X receptor alpha (LXRα) on intestinal cholesterol metabolism was clarified by applying the LXRα inhibitor GSK2033 and siRNA targeting LXRα.

Results

The aortic arch and intestinal villi of the two groups of ApoE−/− mice showed apparent lesions and lipid accumulation, and there were significant changes in a variety of lipids in the plasma and jejunum. Additionally, jejunum LXRα was markedly activated. High cholesterol can significantly activate LXRα in Caco-2 cells. After LXRα was inhibited, the protein level of ATP-binding cassette transporter A1/G5/G8 (ABCA1/G5/G8) decreased, and the quantity and volume of intracellular lipids soared.

Conclusion

In a high-cholesterol environment, the intestine promotes the excretion of cholesterol from the cell through the LXRα-ABCA1/G5/G8 pathway, reduces the intestinal intake of a variety of exogenous cholesterol, and reduces the risk of AS.

Graphical Abstract
Clinical observation of posterior decompression, fusion and fixation in the treatment of spinal gout: a case series
Authors: Zhou M. M. Xingmao , Wu M. M. Minhua , Sang M. M. Lili , Wu M. M. Junzhe
Published: April 2023

Objective

The aim of the present study was to assess the effect of posterior decompression, fusion and fixation in the treatment of spinal gout. Spinal gout is a disease of gouty arthritis involving the spine, which can affect all segments of the spine. At present, the etiology and pathogenesis of spinal gout are not clear, and there are no definite methods for the treatment of spinal gout.

Methods

This was a case series of seven patients (seven men) who underwent posterior decompression, fusion and fixation in the treatment of spinal gout between January 2016 and January 2020. Physical examination, radiography, CT, MRI, Japanese Orthopaedic Association (JOA) score and visual analog scale (VAS) score were used to evaluate the effect of this procedure. All patients were followed up every 3 months. The evaluation time point was 12 months after the operation. Comparisons of the functional indexes of the patients before and after the operation were performed using SPSS 22.0 (IBM, Armonk, NY, USA).

Results

The JOA score was 13.43 ± 6.55 and the VAS score was 7.43 ± 1.51 preoperatively. The JOA score was 24.43 ± 3.74 and the VAS score was 0.86 ± 0.90 postoperatively at 12 months after surgery. At 12 months after surgery, the JOA and VAS score showed significant improvements when compared with those before surgery (P = 0.004 and P = 0.002, respectively). None of the patients had re-surgery of the gout due to actively and reasonably controlling uric acid. No loosening or displacement of screws was reported. There was only one screw tail cap loosening. Radiographic examination revealed that there was no obvious accumulation of gout or surrounding bone destruction, and the segmental instability was significantly improved. There was no progressive aggravation of neurological symptoms of the seven patients.

Conclusions

Posterior approach decompression, fusion and fixation can stabilize the vertebral body, remove gout and directly relieve local spinal cord compression. The method is a reliable surgical choice for the treatment of spinal gout.
Organizational peer support to enable rehabilitating surgical services in Northern Ethiopia
Authors: Kebede Meskerem Aleka , Beyene Andualem , Kedir Nurhusen , Abegaz Bethelhem , Friebel Rocco
Published: April 2023

The ongoing violent conflict in Northern Ethiopia has caused displacement, death, and destruction. Health services infrastructure became one of the primary victims of the war, leaving millions unable to access essential surgical health services at a time when demand for surgical interventions is on the rise. Rehabilitating surgical services was identified as a priority by the federal government, regional health bureaus, and humanitarian organizations, forming an integral part in rebuilding communities after war. Under the auspices of the Federal Ministry of Health of Ethiopia, a hospital twinning program between providers in non-conflict and conflict affected areas was first introduced in December 2021, now including 13 active partnerships. The program builds on a previous best practice gained from the Ethiopian Hospital Alliance for Quality to strengthen local health care providers in regaining capabilities to serve local populations. Field experience of two hospital twinning projects have shown significant scope of organizational peer support at times of crisis, successfully enabling conflict-afflicted hospitals to regain the capacity necessary to re-introduce surgical services. While overcoming challenges such as lack of basic supplies including electricity and blood may be required to further increase the scope of this program in Northern Ethiopia, relative success highlights important lessons for similar approaches in areas affected by conflict, or natural disasters.