bluuebunny/crossref_metadata_2025 huggingface dataset:
Mucoepidermoid carcinoma of the pancreas: A case report and literature review
Authors: Zhang Huan , Wang Shuyan , Wang Chunnian
Published: February 2024

Introduction:

Primary mucoepidermoid carcinoma (MEC) is a common malignant neoplasm of the salivary glands, but is very rare in the pancreas. To date, only 10 cases have been reported in the literature. Because MEC of the pancreas is very rare, there is little information about its diagnosis, treatment, and metastasis. Herein, we present the eleventh case and review the relevant literature.

Patient concerns:

A 65-year-old woman presented with a mass in the body of the pancreas and multiple masses in the liver on abdominal magnetic resonance imaging. The patient initially underwent EUS-guided fine-needle aspiration and was diagnosed with adenocarcinoma. After adjuvant chemotherapy, resection of the pancreatic body and tail was performed, and the tissues were pathologically, histologically, and immunochemically examined. Specific strains and gene rearrangements were analyzed.

Diagnosis:

Mucoepidermoid pancreatic cancer.

Intervention:

After a 4-month course of adjuvant chemotherapy, laparoscopic surgery was performed.

Outcomes:

The patient is alive until the submission of this paper.

Conclusion:

We presented a case of mucoepidermoid pancreatic cancer in a 65-year-old woman. Pathological examination revealed that the tumor parenchyma consisted of 3 cell types. There are mainly epidermoid cells, intermediate cells between the basal and epidermoid cells, and mucus-producing cells in varying proportions. Immunohistochemical staining showed that there were different types of cells with unique morphological characteristics. In summary, primary MECs of the pancreas are rare and have poor prognosis. Few studies have been conducted on the diagnosis, treatment, and metastasis of MECs; therefore, further studies are needed to detect them.
Assessment of clinical prognosis improvement in children with concomitant anterior and posterior urethral valves: A case series report
Authors: Mo Zhiqiang , Zhang Weiping , Sun Ning , Tian Jun , Li Minglei , Song Hongcheng , Xie Xianghui
Published: February 2024

Background:

Concomitant anterior urethral valves (AUVs) and posterior urethral valves (PUVs) is an extremely rare congenital urologic anomaly, which may be easily overlooked in the clinic.

Objective:

This study assessed the prognosis of children with concomitant PUVs and AUVs.

Methods:

The clinical data of inpatients with concomitant AUVs and PUVs in our hospital were collected from January 1983 to June 2022. The clinical manifestations, auxiliary inspection, and treatment were described in detail.

Results:

In total, 6 cases of concomitant AUVs and PUVs in boys were found in our hospital, with ages ranging from 3 months to 9 years; the main clinical manifestation was abnormal urination. Four patients exhibited concomitant AUVs and PUVs preoperatively and underwent simultaneous anterior and posterior urethral valvotomy. Follow-up studies showed that 3 patients’ clinical symptoms substantially improved with well-maintained renal function. One patient died of renal failure. In the other 2 patients, PUVs were initially identified and excised, but their clinical symptoms did not show substantial improvement. Following voiding cystourethrography (VCUG), the AUVs were found and obstructions were then completely relieved. However, 2 patients died of renal failure.

Conclusions:

If urinary symptoms cannot be substantially relieved after posterior urethral valvotomy, VCUG and cystoscopy should be repeated to shorten the interval between anterior and posterior urethral valvotomies to improve patient prognosis.
Long-term debridement effect of denervated large sacrococcygeal pressure injury: A case report
Authors: Lu Yan , Wu Hai-Long , Luo Zong-Jian
Published: February 2024

Rationale:

Complicated pressure injury in paraplegic patients is common and difficult to manage. Previous case studies have documented short-term management; however, little is known regarding suitable approaches to long-term clearing of extensive pressure injury in the sacrococcygeal area under denervation.

Patient concerns:

A 53-year-old man was bedridden for 1.5 years owing to cervical vertebral fracture-dislocation (C5–C6), resulting in extensive sacrococcygeal pressure injury.

Diagnoses:

On admission, he presented with the injury complicated by infection (stage IV necrosis), and his vital signs were unstable.

Interventions:

The infection was treated with a range of antibiotics, including clindamycin phosphate, metronidazole, cefoperazone sodium, and sulbactam sodium. Debridement of the pressure injury was performed, helping remove the necrotic tissue and stimulate tissue regeneration.

Outcomes:

The patient was discharged after 88 days of hospitalization. The extent of the pressure injury at discharge was reduced compared with that at admission. At 4-month follow-up, the injury was nearly healed, with no signs of any further complications.

Lessons:

This case study suggests that wound debridement is a cost-effective and clinically efficacious approach to long-term complicated pressure injury management.
Acupoint herbal patching for postherpetic neuralgia: A systematic review and meta-analysis
Authors: Pu Bingyu , Lu Xiaoxue , Yu Peilin , Wang Chengjie , Li Juan , Yang Dianhui , Wang Jian
Published: February 2024

Background:

This study aimed to systematically evaluate the clinical effectiveness and safety of acupoint herbal patching in the treatment of postherpetic neuralgia.

Methods:

Eight databases including PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, Wan-Fang Database, China Biomedical Literature Service System, and Chongqing VIP Chinese Science were searched. The search time was set to October 2023. Two researchers independently screened the literature according to the inclusion and exclusion criteria; extracted the basic information, acupoints, Chinese herbal medicine, pain score, sleep score, depression score, and other information of the subjects, and independently assessed the risk of bias by 2 researchers. Meta-analysis of the included studies was performed using the StataMP 16 software.

Results:

Fifteen studies with 1362 participants were included in this meta-analysis. Ashi is the acupoint frequency at the forefront, and Borneol is the Chinese herbal medicine frequency at the forefront. The acupoint herbal patching group showed significant improvements in visual analog score (SMD: −2.09; 95% Cl: −2.77, −1.42; P < .001), sleep score (SMD: −1.58; 95% Cl: −2.11, −1.05; P < .001), depression score (SMD: −1.61; 95% Cl: −2.22, −0.99; P < .001), Chinese medicine syndrome score (SMD: −2.32; 95% Cl: −2.84, −1.80; P = .06), dermatology life quality index (weighted mean differences: −4.11; 95% Cl: −4.58, −3.63; P = .98), and related laboratory indicators compared to the control group, and the total effective rate was significantly higher (relative risk: 1.20; 95% confidence interval: 1.15, 1.26; P = .99) than the control group. Two studies reported adverse reactions, but the 2 groups were not statistically significant.

Conclusions:

Acupoint herbal patching intervention in postherpetic neuralgia is effective in improving the pain, sleep, anxiety, depression, quality of life of patients, and related laboratory indicators.
Co-infection of Nocardia and Aspergillus fumigatus in a immunosuppressed patient: Case report
Authors: Wang Lei , Liu Yang , Li Hui
Published: February 2024

Background:

Nocardia and Aspergillus fumigatus are opportunistic pathogenic fungus that has a major impact on the mortality of rheumatoid arthritis patients. Opportunistic infections in immunocompromised patients present diagnostic challenges. Nocardia and A fumigatus are both easily overlooked because of their rarity, leading to delayed diagnosis and treatment.

Case presentation:

We report an infection caused by steroid use in a patient with rheumatoid arthritis. A 76-year-old man with a history of rheumatoid arthritis was admitted to our hospital because of cough, expectoration and fever for 10 days. The patient had low immune function, granulocytopenia, diffuse infiltration could be seen on chest computed tomography, and BAL fluid galactomannan level of 1.3 S/CO. The microbiological findings reflect a possible co-infection with Nocardia and A fumigatus. Voriconazole was used to treat pulmonary aspergillosis, ceftriaxone and Trimethoprim-Sulfamethoxazole were used to treat Nocardia. After timely targeted medication administration, the patient was discharged with a good prognosis.

Conclusion:

Co-infection is more common in immunosuppressed patients and warrants attention in clinical practice. Early diagnosis and treatment can help patients with Co-infection of Nocardia and A fumigatus achieve better prognosis.
A noninvasive treatment for gastro-mediastinal or gastro-pleural fistula after esophagogastrectomy
Authors: Bi Yonghua , Ren Jianzhuang , Han Xinwei
Published: February 2024

Our objective was to assess the safety and efficacy of 3 tubes with or without covered esophageal stent placement for the management of gastro-mediastinal or gastro-pleural fistula. We retrospectively assessed the clinical data of 31 consecutive patients with gastro-mediastinal or gastro-pleural fistula treated by using a noninvasive treatment from February 2013 to July 2022. Patients received 3 tubes (jejunal feeding tube, gastrointestinal drainage tube and abscess drainage tube) with or without esophageal-covered stent placement. All patients received continue abscess drainage and nutritional support after procedure. The tubes and/or esophageal-covered stents were removed after fistula healing. All patients received 3 tubes placement and 11 patients with luminal narrowing received esophageal covered stent placement. Technically success was found in all patients, with no procedure-related death, esophageal rupture or massive hemorrhage. Abscess cavity disappeared in 22 patients, with a clinical success rate of 71.0%. All patients received esophageal stent placement were cured and stents were removed, for a median duration of 1.6 months (interquartile ranges [IQR] 1.4, 3.7). Three patients showed clinical improved, with markedly decreased abscess cavity and markedly shrunk fistula. The median survival was 30.8 months. The 1-, 3-, 5-year survival rates were 71.1%, 46.1% and 39.5%, respectively. A noninvasive treatment of 3 tubes with or without covered esophageal stent placement is safe and effective for gastro-mediastinal or gastro-pleural fistula after esophagogastrectomy.
Comparison of clinical and economic evaluation between selected generic and original febuxostat tablets in Chinese gout patients with hyperuricemia: A real-world multicenter retrospective study
Authors: Si Xia , Huang Lin , Ding Qingming , Zhang Wei , Zhao Rui , Ai Chao , An Zhuoling , Liu Gang , Zhang Chunyan , Zhong Xue , Feng Yufei
Published: February 2024

Generic febuxostat tablets were listed in China’s third-round centralized drug procurement program. However, there are no sufficient data available on the use of febuxostat in a real-world setting. This study aimed to compare the efficacy, safety, and cost of selected generic febuxostat with original febuxostat in primary gout and hyperuricemia. Medical records at 3 tertiary hospitals from January 2014 to February 2022 were retrospectively analyzed. Propensity score matching was used to balance the distribution of baseline characteristics. The proportion of patients achieving target serum uric acid (SUA) levels at 12 weeks, the percent changes from baseline in SUA, adverse drug reactions, and the cost of febuxostat therapy were assessed. A total of 221 patients were recruited and 57 pairs of patients were 1:1 matched in the 2 groups. There was no statistically significant difference in the proportion of patients achieving a target SUA levels below 300 μmol/L, the percent changes of SUA decreased from baseline, and the incidence of adverse drug reactions between the 2 groups (all P > .05). The daily febuxostat cost in the generic group were significantly lower than that in original group (P < .05). Based on the results of this study, the clinical efficacy of selected generic febuxostat is comparable to that of original febuxostat for gout with hyperuricemia. No serious adverse reactions were reported in the 2 groups, and generic febuxostat is more economical than the original febuxostat.
Identification of potential biomarkers in the peripheral blood of neonates with bronchopulmonary dysplasia using WGCNA and machine learning algorithms
Authors: Luo Liyan , Luo Fei , Wu Chuyan , Zhang Hong , Jiang Qiaozhi , He Sixiang , Li Weibi , Zhang Wenlong , Cheng Yurong , Yang Pengcheng , Li Zhenghu , Li Min , Bao Yunlei , Jiang Feng
Published: February 2024

Bronchopulmonary dysplasia (BPD) is often seen as a pulmonary complication of extreme preterm birth, resulting in persistent respiratory symptoms and diminished lung function. Unfortunately, current diagnostic and treatment options for this condition are insufficient. Hence, this study aimed to identify potential biomarkers in the peripheral blood of neonates affected by BPD. The Gene Expression Omnibus provided the expression dataset GSE32472 for BPD. Initially, using this database, we identified differentially expressed genes (DEGs) in GSE32472. Subsequently, we conducted gene set enrichment analysis on the DEGs and employed weighted gene co-expression network analysis (WGCNA) to screen the most relevant modules for BPD. We then mapped the DEGs to the WGCNA module genes, resulting in a gene intersection. We conducted detailed functional enrichment analyses on these overlapping genes. To identify hub genes, we used 3 machine learning algorithms, including SVM-RFE, LASSO, and Random Forest. We constructed a diagnostic nomogram model for predicting BPD based on the hub genes. Additionally, we carried out transcription factor analysis to predict the regulatory mechanisms and identify drugs associated with these biomarkers. We used differential analysis to obtain 470 DEGs and conducted WGCNA analysis to identify 1351 significant genes. The intersection of these 2 approaches yielded 273 common genes. Using machine learning algorithms, we identified CYYR1, GALNT14, and OLAH as potential biomarkers for BPD. Moreover, we predicted flunisolide, budesonide, and beclomethasone as potential anti-BPD drugs. The genes CYYR1, GALNT14, and OLAH have the potential to serve as diagnostic biomarkers for BPD. This may prove beneficial in clinical diagnosis and prevention of BPD.
All shook up: how the COVID-19 pandemic rocked pediatric asthma care
Authors: Kaplan Carl , Christophides Alexa H. , Kranidis Alexandra M. , Saint-Fleur Ashley L. , Kier Catherine
Published: February 2024

Purpose of review

Asthma management is a crucial aspect of public health. The landscape of asthma management underwent significant change in the wake of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. These changes greatly affected existing patients, individuals suffering with undiagnosed illness, providers, and the healthcare system as a whole.

Recent findings

Providers had to navigate through the potential risk of exposure while weighing the benefit of office visits for patients. This promoted the rapid uptake of telemedicine and virtual outreach, as well as modifications to acute management and controller therapies. Telehealth allowed for the remote monitoring of these patient populations, increased compliance with home-based self-management, and an emphasis on patient education. Furthermore, the pandemic underscored the importance of proactive asthma management as many individuals were left untreated or undiagnosed for various reasons. It is evident that the SARS-CoV-2 pandemic reshaped the landscape of various components of the healthcare system, including asthma management, necessitating innovative approaches to monitoring and patient education.

Understanding the lessons learned from this time period is crucial for enhancing the resilience of our health system in the wake of future challenges that may be posed against our system
Approach to acute agitation in the pediatric emergency department
Authors: Foster Ashley A. , Saidinejad Mohsen , Li Joyce
Published: February 2024

Purpose of review

The complexity of pediatric mental and behavioral health (MBH) complaints presenting to emergency departments (EDs) is increasing at an alarming rate. Children may present with agitation or develop agitation during the ED visit. This causes significant distress and may lead to injury of the child, caregivers, or medical staff. This review will focus on providing safe, patient-centered care to children with acute agitation in the ED.

Recent findings

Approaching a child with acute agitation in the ED requires elucidation on the cause and potential triggers of agitation for optimal management. The first step in a patient-centered approach is to use the least restrictive means with behavioral and environmental strategies. Restraint use (pharmacologic or physical restraint) should be reserved where these modifications do not result in adequate de-escalation. The provider should proceed with medications first, using the child's medication history as a guide. The use of physical restraint is a last resort to assure the safety concerns of the child, family, or staff, with a goal of minimizing restraint time.

Children are increasingly presenting to EDs with acute agitation. By focusing primarily on behavioral de-escalation and medication strategies, clinicians can provide safe, patient-centered care around these events.
Sexual behaviours and risk with women in MSM in sub-Saharan Africa
Authors: Fiorentino Marion , Yanwou Nathan , Gravier-Dumonceau Mazelier Robinson , Eubanks August , Roux Perrine , Laurent Christian , Spire Bruno
Published: February 2024

In sub-Saharan Africa (SSA), MSM – a high HIV prevalence group – experience strong social stigma and pressure to have female partners. Accordingly, they could constitute a bridging group for HIV transmission to cisgender women. We developed a multilevel summary of MSM sexual behaviors and risk with women in various SSA regions. Following PRISMA guidelines, we conducted a mixed-method systematic review of data of sex with women in MSM in SSA. We performed meta-analyses on quantitative data (i.e. percent of recent sex and condomless sex with women) for each SSA region (when proportions reported in ≥4 studies). Pooled proportions were calculated using random-effects models. Qualitative data were analyzed using the three-step thematic synthesis methodology. The pooled proportion of MSM who had sex with women was 58% (33–83%) in East Africa (in the previous 3 months), and 27% (13–48%) in Southern Africa and 50% (95% CI 39–62%) in West Africa (in the previous 6 months); 23% (16–32%) of MSM in West Africa had condomless sex with a woman (during the most recent encounter). Approximately one quarter of MSM had recent multiple female partners. MSM reported having sex with women because of heteronormative pressure, erotic/romantic attraction, or financial needs leading to transactional sex. MSM may act as a bridging population to women in SSA, as they commonly practice sex with women and risky sexual behaviors with them. HIV programmes and community-based support for MSM should be adapted to this population to reduce this risk.
Modified Technique for Auricular Helical Rim Reconstruction in Adult Patients with Subtotal Helical Rim Defects
Authors: Lashin Riham , Elshahat Ahmed
Published: February 2024

Background:

In adults, the volume of costal cartilage is enough for reconstruction, but floating cartilage is hard, brittle, and easily broken due to calcification, in addition to being short, making it unsuitable for helical rim reconstruction in such age groups.

Aim of Study:

This study describes a novel technique in which adult patients underwent 2-stage helical rim reconstruction using the syncytium of sixth and seventh costal cartilage.

Material and Methods:

A single-arm clinical trial involves 35 adults with total and subtotal helical rim defects, either congenital, post-traumatic, postburn, or postvascular malformation excision. Twenty-nine unilateral and 6 bilateral cases. The age of patients ranged between 19 and 40 years. In the period between April 2021 and April 2023. Follow-up was 6 months.

Results:

There were no technique-related complications, such as broken helix. In most cases, scars were invisible, with the normal contour of helical rim. Among the 35 patients, 19 were graded as excellent, 13 as good, and 3 as fair. In objective photographic evaluation, all patients were evaluated with high (3 or 4) ratings; the score was 3 in 19 patients and 4 in 16 patients. All patients were satisfied with the size, contour, position and details of the new helix.

Conclusion:

Using the syncytium of the sixth and seventh costal cartilage to fabricate the helical rim in adult patients gives a suitable volume of cartilage graft as regards the length and width, which suits the reconstruction of the helical rim, and shows a good configuration with satisfactory surgical results.
A Novel Oligonucleotide mRNA Mimic Attenuates Hemorrhage-Induced Acute Lung Injury
Authors: Hu Zhijian , Li Jingsong , Zhang Fangming , Jacob Asha , Wang Ping
Published: February 2024

Hemorrhagic shock (HS) is accompanied by a pronounced activation of the inflammatory response in which acute lung injury (ALI) is one of the most frequent consequences. Among the pivotal orchestrators of this inflammatory cascade, extracellular cold-inducible RNA-binding protein (eCIRP) emerges as a noteworthy focal point, rendering it as a promising target for the management of inflammation and tissue injury. Recently, we have reported that oligonucleotide poly(A) mRNA mimic termed A12selectively binds to the RNA binding region of eCIRP and inhibits eCIRP binding to its receptor TLR4. Furthermore, in vivo administration of eCIRP induces lung injury in healthy mice and that mouse deficient in CIRP showed protection from inflammation associated lung injury. We hypothesize that A12inhibits systemic inflammation and acute lung injury in hemorrhagic shock. To test the impacts of A12on systemic and lung inflammation, extent of inflammatory cellular infiltration and resultant lung damage were evaluated in a mouse model of hemorrhagic shock. Male mice were subjected to controlled hemorrhage with a mean arterial pressure of 30 mmHg for 90 min and then resuscitated with Ringer’s Lactate solution containing phosphate buffered saline (Vehicle) or A12at a dose of 4 nmol/g body weight (treatment). The infusion volume was twice that of the shed blood. At 4 h after resuscitation, mice were euthanized, blood and lung tissues were harvested. Blood and tissue markers of inflammation and injury were evaluated. Serum markers of injury (LDH, ALT and BUN) and inflammation (TNF-α, IL-6) were increased after HS and A12treatment significantly decreased their levels. A12treatment also decreased lung levels of TNF-α, MIP-2 and KC mRNA expressions. Lung histological injury score, neutrophil infiltration (Ly6G staining and myeloperoxidase (MPO) activity), and lung apoptosis were significantly attenuated after A12treatment. Our study suggests the capacity of A12in attenuating HS-induced ALI and may provide novel perspectives in developing efficacious pharmaceutics for improving hemorrhage prognosis.
The Carer Assessment of MedicaTion Management GuidanCe for People With Dementia at Hospital Discharge (CATCH) Tool
Authors: Sawan Mouna , Clough Alexander , Mirzaei Ardalan , Widjaja Gabrielle J. , Schneider Carl , Jeon Yun-Hee , Chen Timothy , Hilmer Sarah N. , Gnjidic Danijela
Published: February 2024

Purpose:

The Carer Assessment of medicaTion management guidanCe for people with dementia at Hospital discharge (CATCH) tool was developed to examine the carer’s experiences of medication management guidance delivery at discharge. This study explored its factor structure, characterized carers’ experiences at discharge, and identified predictors of carer preparedness to manage medications at discharge.

Methods:

A cross-sectional survey of carers across Australia was distributed. Survey responses were analyzed descriptively, and exploratory factor and regression analyses were performed.

Results:

A total of 185 survey responses were completed. Exploratory factor analysis revealed 2 factors in the CATCH tool: (1) shared and supported decision-making in medication management (16 items loading 0.47 to 0.93); 2) provision of medication management guidance that is easy to understand (4 items loading (0.48 to 0.82). Internal consistency was acceptable (Cronbach alpha >0.8). Almost 18% of participants stated that they were not included in decisions about medications for people with dementia. The carer reported that the measure of how guidance is provided was positively related to their confidence in the management of medications postdischarge and satisfaction (P< 0.05 for both).

Conclusions:

The CATCH tool can give the patient and carer an opportunity to provide feedback on key elements of medication management guidance delivered at discharge.
Compassion Versus Accuracy
Authors: Kent Katrina , Adly Ibrahim Nesrine , Romero Kristoffer , Baker Shannon , Greenacre Matthew , Boucher Chantal M. , Roth Robert M. , Erdodi Laszlo A.
Published: February 2024

The Mini-mental State Examination (MMSE) is a commonly used screening tool for cognitive impairment. Lenient scoring of spatial orientation errors (SOEs) on the MMSE is common and negatively affects its diagnostic utility. We examined the effect of lenient SOE scoring on MMSE classification accuracy in a consecutive case series of 103 older adults (age 60 or above) clinically referred for neuropsychological evaluation. Lenient scoring of SOEs on the MMSE occurred in 53 (51.4%) patients and lowered the sensitivity by 7% to 18%, with variable gains in specificity (0% to 11%) to psychometrically operationalized cognitive impairment. Results are consistent with previous reports that lenient scoring is widespread and attenuates the sensitivity of the MMSE. Given the higher clinical priority of correctly detecting early cognitive decline over specificity, a warning against lenient scoring of SOEs (on the MMSE and other screening tools) during medical education and in clinical practice is warranted.
Differentiating Pathologic from Physiologic Fibrinolysis: Not as Simple as Conventional Thrombelastography
Authors: Moore Hunter B , Barrett Christopher D , Moore Ernest E , Pieracci Fredric M , Sauaia Angela
Published: February 2024

BACKGROUND:

Conventional rapid thrombelastography (rTEG) cannot differentiate fibrinolysis shutdown from hypofibrinolysis, as both of these patient populations have low fibrinolytic activity. Tissue plasminogen activator (tPA) TEG can identify depletion of fibrinolytic inhibitors, and its use in combination with rTEG has the potential to differentiate all 3 pathologic fibrinolytic phenotypes after trauma. We hypothesize tPA-TEG and rTEG in combination can further stratify fibrinolysis phenotypes postinjury to better stratify risk for mortality.

STUDY DESIGN:

Adult trauma patients (981) with both rTEG and tPA-TEG performed less than 2 hours postinjury were included. rTEG lysis at 30 minutes after maximum amplitude (LY30) was used to initially define fibrinolysis phenotypes (hyperfibrinolysis >3%, physiologic 0.9% to 3%, and shutdown <0.9%), with Youden Index then used to define pathologic extremes of tPA-TEG LY30 (tPA sensitive [depletion of fibrinolytic inhibitors] vs resistant) resulting in 9 groups that were assessed for risk of death.

RESULTS:

The median New Injury Severity Score was 22, 21% were female, 45% had penetrating injury, and overall mortality was 13%. The tPA-TEG LY30 inflection point for increased mortality was >35.5% (tPA sensitive, odds ratio mortality 9.2, p < 0.001) and <0.3% (tPA resistance, odds ratio mortality 6.3, p = 0.04). Of the 9 potential fibrinolytic phenotypes, 5 were associated with increased mortality. Overall, the 9 phenotypes provided a significantly better prediction of mortality than rTEG or tPA-TEG alone (areas under the operating characteristics curves = 0.80 vs 0.63 and 0.75, respectively, p < 0.0001). These could be condensed to 3 pathologic phenotypes (true hyperfibrinolysis, early fibrinolysis shutdown, and hypofibrinolysis).

CONCLUSIONS:

The combination of rTEG and tPA-TEG increases the ability to predict mortality and suggests patient-specific strategies for improved outcomes.
Highly accurate discovery of terpene synthases powered by machine learning reveals functional terpene cyclization in Archaea
Authors: Samusevich Raman , Hebra Téo , Bushuiev Roman , Bushuiev Anton , Čalounová Tereza , Smrčková Helena , Chatpatanasiri Ratthachat , Kulhánek Jonáš , Perković Milana , Engst Martin , Tajovská Adéla , Sivic Josef , Pluskal Tomáš
Published: February 2024

Terpene synthases (TPSs) generate the scaffolds of the largest class of natural products, including several first-line medicines. The amount of available protein sequences is increasing exponentially, and accurate computational characterization of their function remains an unsolved challenge. We assembled a curated dataset of one thousand characterized TPS reactions and developed a method to devise highly accurate machine-learning models for functional annotation in a low-data regime. Our models significantly outperform existing methods for TPS detection and substrate prediction. By applying the models to large protein sequence databases, we discovered seven TPS enzymes previously undetected by state-of-the-art protein signatures and experimentally confirmed their activity, including the first reported TPSs in the major domain of life Archaea. Furthermore, we discovered a new TPS structural domain and distinct subtypes of previously known domains. This work demonstrates the potential of machine learning to speed up the discovery and characterization of novel TPSs.
Structured Expert Judgement Approach of the Health Impact of Various Chemicals and Classes of Chemicals
Authors: Marti Deniz , Hanrahan David , Sanchez-Triana Ernesto , Wells Mona , Corra Lilian , Hu Howard , Breysse Patrick N. , Laborde Amalia , Caravanos Jack , Bertollini Roberto , Porterfield Kate , Fuller Richard
Published: February 2024

Introduction

Chemical contamination and pollution are an ongoing threat to human health and the environment. The concern over the consequences of chemical exposures at the global level continues to grow. Because resources are constrained, there is a need to prioritize interventions focused on the greatest health impact. Data, especially related to chemical exposures, are rarely available for most substances of concern, and alternate methods to evaluate their impact are needed.

Structured Expert Judgment (SEJ) Process

A Structured Expert Judgment3process was performed to provide plausible estimates of health impacts for 16 commonly found pollutants: asbestos, arsenic, benzene, chromium, cadmium, dioxins, fluoride, highly hazardous pesticides (HHPs), lead, mercury, polycyclic-aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs), Per- and Polyfluorinated Substances (PFAs), phthalates, endocrine disrupting chemicals (EDCs), and brominated flame retardants (BRFs). This process, undertaken by sector experts, weighed individual estimations of the probable global health scale health impacts of each pollutant using objective estimates of the expert opinions’ statistical accuracy and informativeness.

Main Findings

The foremost substances, in terms of mean projected annual total deaths, were lead, asbestos, arsenic, and HHPs. Lead surpasses the others by a large margin, with an estimated median value of 1.7 million deaths annually. The three other substances averaged between 136,000 and 274,000 deaths per year. Of the 12 other chemicals evaluated, none reached an estimated annual death count exceeding 100,000. These findings underscore the importance of prioritizing available resources on reducing and remediating the impacts of these key pollutants.

Range of Health Impacts

Based on the evidence available, experts concluded some of the more notorious chemical pollutants, such as PCBs and dioxin, do not result in high levels of human health impact from a global scale perspective. However, the chemical toxicity of some compounds released in recent decades, such as Endocrine Disrupters and PFAs, cannot be ignored, even if current impacts are limited. Moreover, the impact of some chemicals may be disproportionately large in some geographic areas. Continued research and monitoring are essential; and a preventative approach is needed for chemicals.

Future Directions

These results, and potential similar analyses of other chemicals, are provided as inputs to ongoing discussions about priority setting for global chemicals and pollution management. Furthermore, we suggest that this SEJ process be repeated periodically as new information becomes available.
Computational basis of hierarchical and counterfactual information processing
Authors: Ramadan Mahdi , Tang Cheng , Watters Nicholas , Jazayeri Mehrdad
Published: February 2024

Cognitive theories attribute humans’ unparalleled capacity in solving complex multistage decision problems to distinctive hierarchical and counterfactual reasoning strategies. Here, we used a combination of human psychophysics and behaviorally-constrained neural network modeling to understand the computational basis of these cognitive strategies. We first developed a multi-stage decision-making task that humans solve using a combination of hierarchical and counterfactual processing. We then used a series of hypothesis-driven behavioral experiments to systematically dissect the potential computational constraints that underlie these strategies. One experiment revealed that humans have limited capacity for parallel processing. Another indicated that counterfactuals do not fully compensate for this limitation because of working memory limits. A third experiment revealed that the degree to which humans use counterfactuals depends on the fidelity of their working memory. Next, we asked whether the strategies humans adopt are computationally rational; i.e., optimal under these constraints. To do so, we analyzed the behavior of a battery of task-optimized recurrent neural networks (RNNs) that were subjected to one or more of these constraints. Remarkably, only RNNs that were subjected to all these constraints behaved similarly to humans. Further analysis of the RNNs revealed that what cognitive theories posit as distinctive strategies such as hierarchical and counterfactual are subdivisions in a continuum of computationally rational solutions that includes optimal, counterfactual, postdictive, and hierarchical.
SRP19and the protein secretion machinery is a targetable vulnerability in cancers withAPCloss
Authors: Xi Xinqi , Liu Ling , Tuano Natasha , Tailhades Julien , Mouradov Dmitri , Sieber Oliver , Cryle Max , Segelov Eva , Rosenbluh Joseph
Published: February 2024

Adenomatous Polyposis Coli (APC) is a tumour suppressor that is frequently lost in colorectal and other cancers. A common mechanism forAPCloss includes heterozygousAPCdeletion. Here, we show thatSRP19, is located nearAPCand is often co-deleted in these tumours. HeterozygousAPC/SRP19loss leads to lower levels ofSRP19mRNA and protein. Consequently, cells withAPC/SRP19loss are vulnerable to partial suppression ofSRP19. We show thatSRP19loss is a unique vulnerability sinceSRP19is rate limiting for the formation of the Signal Recognition Particle (SRP), a complex that mediates translocation of proteins to the ER. Consistent with these observations, partialSRP19knock-down or low dose Arsenic Trioxide treatment induces ER stress and inhibits proliferation inAPC/SRP19loss cancers. Our work identifies a new strategy to treat cancers withAPC/SRP19heterozygous deletions and provides a framework for identifying vulnerabilities associated with loss of a tumour suppressor.
Association between human blood metabolome and the risk of coronary heart disease: Mendelian randomization study
Authors: Zhu Jia , Xia Xiaojun , Jiang Haodong , Wang Congying , Jin Yunpeng
Published: February 2024

In this study, we employed Mendelian Randomization (MR) to elucidate the causal relationships between specific blood metabolites and Coronary Heart Disease (CHD). By analyzing data from Genome-Wide Association Studies (GWAS) and the FinnGen database, we conducted a two-sample MR analysis focusing on 40 metabolites and 6 metabolite ratios linked to CHD risk. Our findings highlight a group of metabolites significantly influencing CHD risk, either augmenting or mitigating it. Rigorous sensitivity checks, including MR-Egger and MR-PRESSO, negated the influence of horizontal pleiotropy and reinforced the robustness of our results. Furthermore, reverse MR analysis unveiled a bidirectional influence between certain metabolites and CHD, suggesting a complex mutual interaction. This study not only unravels intricate connections between metabolites and CHD, but also paves the way for potential biomarkers instrumental in CHD prevention and therapy. However, it acknowledges certain limitations, such as the modest sample size and a primary focus on European genetic data, underscoring the need for further investigations in more diverse population cohorts.
Functionally distinct dopamine domains in the hippocampus
Authors: Mehra Muneshwar , Molina Gerardo , Islam Md Tarikul , Dhanerawala Zahra M. , Bano Eleonora , Han Edward B.
Published: February 2024

Numerous studies have identified dopamine signaling in the hippocampus as necessary for certain types of learning and memory. Since dopamine in the striatum is strongly tied to rewards, dopamine in the hippocampus is thought to reinforce reward learning. Despite the critical influence of dopamine on hippocampal function, little is known about dopamine release in the hippocampus or the specific ways dopamine can influence hippocampal function. Based on the functional complexity of hippocampal circuitry, we hypothesized the existence of multiple dopamine signaling domains. Using optical dopamine sensors, two-photon imaging, and head-fixed behaviors, we identified two functionally and spatially distinct dopamine domains in the hippocampus. The “superficial” domain (cell somata and apical dendrites) showed reward-related dopamine transients early in Pavlovian conditioning but were replaced by “deep” domain transients (basal dendritic layer) with experience. These two domains also play distinct roles in a hippocampal-dependent, goal-directed virtual reality task where mice use exploratory licks to discover the location of a hidden reward zone. Here, positive dopamine ramps appeared in the superficial domain as mice approached the reward zone, similar to those seen in the striatum. At the same time, the deep domain showed strong reward-related transients. These results reveal small-scale, anatomically segregated, dopamine domains in the hippocampus. Furthermore dopamine domain activity had temporal-specificity for different phases of behavior. Finally, the subcellular scale of dopamine domains suggests specialized postsynaptic pathways for processing and integrating functionally distinct dopaminergic influences.
WITHDRAWN: Sex-dependent effects ofSetd1ahaploinsufficiency on development and adult behaviour
Authors: Bosworth Matthew L. , Isles Anthony R. , Wilkinson Lawrence S. , Humby Trevor
Published: February 2024

Withdrawal Statement

The authors have withdrawn this manuscript due to a duplicate posting of manuscript number BIORXIV/2021/471949. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author. The correct preprint can be found at doi: 10.1101/2021.12.10.471949.
Exploring the drivers of AI-seeking intention among AI community canteen customers
Authors: Wu Hung-Che , Chen Sharleen X. , Xu Haonan
Published: February 2024

Purpose

The purpose of the present research is to address the issue by conceptualizing artificial intelligence (AI) experience quality and its dimensions, and furthermore, to empirically test the relationships among AI experience quality, positive affective reactions, AI experience satisfaction and AI-seeking intention.

Design/methodology/approach

The data were collected from an AI community canteen in Shanghai. They were also analyzed using exploratory and confirmatory factor analyses (EFA and CFA) and structural equation modeling (SEM).

Findings

Four primary dimensions and 15 sub-dimensions of AI experience quality for community canteens were identified. The hypothesized paths between the higher-order constructs – AI experience quality, positive affective reactions, AI experience satisfaction and AI-seeking intention – were confirmed as well.

Originality/value

This is the first study to synthesize AI experience quality, positive affective reactions, AI experience satisfaction and AI-seeking intention in an AI restaurant setting.
Does work meaningfulness hold the key? Exploring the power of meaningful work in attenuating burnout
Authors: Chakravorty Arjun , Kumar Vibhash , Singh Pankaj , Baburaj Sharath
Published: February 2024

Purpose

The paper aims to focus on underpinning the moderating role of work meaningfulness in alleviating the impact of general job demands on burnout directly and via work–family conflict by drawing on the conservation of resources theory.

Design/methodology/approach

Survey methodology was used for this study, using standardized instruments to assess general job demands, meaningfulness, work–family conflict and burnout. The survey was administered to school teachers (n= 800), and the data set was analyzed through SmartPLS 4.0.

Findings

This study ascertained that work meaningfulness moderated the relationship between general job demands and burnout. This study also found that general job demands under conditions of low work meaningfulness positively affected burnout through work–family conflict, thereby validating the moderated mediation model.

Originality/value

While several studies have established the relationship between general job demands, work–family conflict and burnout, to the best of the authors’ knowledge, this is the first study that examined the moderating role of work meaningfulness in the relationship, where work meaningfulness has emerged as a suitable moderator in lowering the impact of job demands on burnout via a work–family conflict. This study contributes to the extant literature on work meaningfulness and adds utility to practice.
Entropy generation for thermo-magnetic fractional order convective flow in complex porous enclosures: a numerical study
Authors: Parmar Deepika , Krishna Murthy S.V.S.S.N.V.G. , Rathish Kumar B.V. , Kumar Sumant
Published: February 2024

Purpose

This study aims to analyze the impact of fractional derivatives on heat transfer and entropy generation during transient free convection inside various complex porous enclosures, such as triangle, L-shape and square-containing wavy surfaces. These porous enclosures are saturated with Cu-water nanofluid and subjected to the influence of a uniform magnetic field.

Design/methodology/approach

In the present study, Darcy’s model is used for the momentum transport equation in the porous matrix. Additionally, the Caputo time fractional derivative is introduced in the energy equation to assess the heat transfer phenomenon. Furthermore, the total entropy generation has been computed by combining the entropy generation due to fluid friction (Sff), heat transfer (Sht) and magnetic field (Smf). The complete mathematical model is further simulated using the penalty finite element method, and the Caputo time derivative term is approximated using the L1 scheme. The study is conducted for various ranges of the Rayleigh number

(102≤Ra≤104), Hartmann number

(0≤Ha≤20) and fractional order parameter

(0<α<1) with respect to time.

Findings

It has been observed that the fractional order parameter α governs the characteristics of entropy generation and heat transfer within the selected range of parameters. The Bejan number associated with heat transfer (Beht), fluid friction (Beff) and magnetic field (Bemf) further demonstrate the dominance of flow irreversibilities. It becomes evident that the initial evolution state of streamlines, isotherms and local entropy varies according to the choice of α. Additionally, increasing Ra values from 102 to 104 shows that the heat transfer rate increases by 123.8% for a square wavy enclosure, 7.4% for a triangle enclosure and 69.6% for an L-shape enclosure. Moreover, an increase in the value of Ha leads to a reduction in heat transfer rates and entropy generation. In this case,

Bemf→1 shows the dominance of the magnetic field irreversibility in the total entropy generation.

Practical implications

Recently, fractional-order models have been widely used to express numerous physical phenomena, such as anomalous diffusion and dispersion in complex viscoelastic porous media. These models offer a more accurate representation of physical reality that classical models fail to capture; this is why they find a broad range of applications in science and engineering.

Originality/value

The fractional derivative model is used to illustrate the flow pattern, heat transfer and entropy-generating characteristics under the influence of a magnetic field. Furthermore, to the best of the author’s knowledge, a fractional-derivative-based mathematical model for the entropy generation phenomenon in complex porous enclosures has not been previously developed or studied.
Sustainable development practices in small and medium-sized enterprises: multiple case studies
Authors: Nabais Etelvina , Franco Mário
Published: February 2024

Purpose

This study aims to understand the sustainable development of small and medium-sized enterprises (SMEs), analysing their current practices in the social, environmental and economic domain.

Design/methodology/approach

To fulfil this objective, an exploratory, qualitative approach was adopted, using the multiple case study methodology and focusing on eight cases (SMEs) in Portugal. Data were collected through interviews, since this technique allows proximity and interaction with decision makers and those responsible for firms’ sustainability.

Findings

From content analysis of the interviews held, the results show that SMEs are aware of and committed to sustainability and that the external context and some of its particularities have a significant impact on their sustainable development. These SMEs undertake various practices of a social, environmental and economic nature, highlighting especially environmental ones such as efficient resource consumption, using more sustainable resources, recycling waste and waste management.

Practical implications

This study contributes greater knowledge of the phenomenon of SMEs’ sustainable development and identifies practical examples that could increase this firm segment’s awareness of the importance of sustainable practices associated with developing their business.

Originality/value

In this study, new and innovative sustainability practices are presented in the SMEs. The authors can underline that this study contributes to reinforcing the theory about the topic investigated by adding knowledge about sustainable development in the SME context. It deepens knowledge in this scientific area, which can be spread in the scientific community and among SMEs.