bluuebunny/crossref_metadata_2025 huggingface dataset:
Manifestation of leech infestation as severe gastrointestinal bleeding in a 3-year-old boy: a case report and review of the literature
Authors: Reihani Hamid , Ghanei-Shahmirzadi Ali , Salehi Sara , Ansari-Charsoughi Narges , Karbasian Fereshteh , Imanieh Mohammad-Hadi
Published: December 2022

Background

Leeches are a class of hermaphroditic parasites that can attach to various body parts and start sucking blood. Gastrointestinal (GI) bleeding due to leeches is a rare phenomenon that is more common in less developed countries. Common symptoms include melena, hematemesis, pallor, weakness, and fatigue. Due to the similar symptoms of this issue to the main differential diagnoses of GI bleeding in pediatrics, such as diarrhea, constipation, diverticulitis, esophagitis, and anal fissures, it is challenging to differentiate it from the rest.

Case presentation

We present a three-year-old boy who was transferred to our center with hematemesis, tarry stool, and a drop in hemoglobin level. He finally was diagnosed with a leech in his stomach.

Conclusions

In less developed counties, the inability to reach safe drinking water, swim in lakes or springs, and inadequate awareness of public health information among individuals can be risk factors for leech infestation.
Social COmmunication Program supported by E-health (SCOPE) for infants and toddlers at elevated likelihood of autism spectrum disorder: study design of a cluster randomized controlled trial
Authors: Snijder Michelle I. J. , Dietz Claudine , van Andel Mieke , Ruiter Emilie L. M. , Buitelaar Jan K. , Oosterling Iris J.
Published: December 2022

Background

Although the importance of early detection and early intervention of autism spectrum disorders (ASD) is widely recognized, multiple barriers exist in accessing early intervention services. As an alternative to these barriers, the SCOPE project presents a new, easy accessible and blended intervention called BEAR (Blended E-health for children at eArly Risk). This paper describes this BEAR intervention and study design of an ongoing two arm cluster randomized controlled trial (RCT).

Methods

BEAR (Blended E-health for children at eArly Risk) is a blended e-health intervention, based on evidence-based naturalistic developmental behavioral interventions (NDBI’s) and can be offered to parents and infants/toddlers at high likelihood for ASD. During the ongoing RCT,N = 88 high risk infants and toddlers will be cluster randomized over the BEAR intervention and care-as-usual (CAU) conditions. The finalized version of the intervention protocol and study design are presented in this paper. The primary outcome measure isjoint engagementmeasured by the Joint Engagement Rating Inventory (JERI) during videotaped parent–child interaction. Secondary outcome measures include severity of ASD symptoms, global level of adaptive functioning, parental well-being, parental skills and satisfaction with healthcare. Also, costs will be estimated from society's perspective. Assessments take place at the start of the study (T1), after eight weeks (T2) and after six months (T3) and include behavioral home observations and parental questionnaires.

Discussion

The SCOPE project aims to contribute to improved early identification and timely start of suitable interventions for infants and toddlers at elevated likelihood for ASD. This ongoing RCT will offer insight in the feasibility, short-term and six months effects of the innovative BEAR intervention. It is estimated that inclusion for the trial (N = 88) is completed in spring 2023.

Trial registration

Dutch Trial Register, NTR7695. Registered at December 17th, 2018,www.trialregister.nl.
Assessing the expression of two post-transcriptional BDNF regulators, TTP and miR-16 in the peripheral blood of patients with Schizophrenia
Authors: Asadi Mohammad Reza , Gharesouran Jalal , Sabaie Hani , Moslehian Marziyeh Sadat , Dehghani Hossein , Arsang-Jang Shahram , Taheri Mohammad , Mortazavi Deniz , Hussen Bashdar Mahmud , Sayad Arezou , Rezazadeh Maryam
Published: December 2022

Schizophrenia (SCZ) is a severe mental disorder with an unknown pathophysiology. Brain-Derived Neurotrophic Factor (BDNF) is a neurotrophin that has been associated with synapse plasticity, learning, and memory, as well as neurodevelopment and neuroprotection. The importance of neurodevelopmental and neurotoxicity-related components in the pathophysiology of SCZ has been highlighted in research on the neurobiology of this disease. The purpose of this research is to investigate the significant expression of two variables, tristetraprolin (TTP) and miR-16, which are known to be regulators of BDNF expression. Fifty Iranian Azeri SCZ patients were enrolled, and fifty healthy volunteers were age- and gender-matched as controls. A quantitative polymerase chain reaction measured the expression levels of the TTP and miR-16 in the peripheral blood (PB) of SCZ patients and healthy people. TTP expression levels in patients were higher than in controls, regardless of gender or age (posterior beta = 1.532, adjustedP-value = 0.012). TTP and miR-16 expression levels were found to be significantly correlated in both SCZ patients and healthy controls (r = 0.701,P < 0.001 andr = 0.777,P < 0.001, respectively). Due to the increased expression of TTP in SCZ and the existence of a significant correlation between TTP and miR-16, which helps to act on target mRNAs with AU-rich elements, this mechanism can be considered an influencing factor in SCZ.
The relationship between changes in the korean fertility rate and policies to encourage fertility
Authors: Jeong Kyuhyoung , Yoon Jiyeon , Cho Heeran J. , Kim Sunghee , Jang Jihyun
Published: December 2022

Background

Korean government has established various policies to counter the low fertility rate since the mid-2000s, but it still has the lowest fertility rate among OECD member countries. This study investigated the relationship between changes in the Korean fertility rate and policies to encourage fertility.

Methods

This study utilized data of the total fertility rate of 250 local governments between 2014 and 2018, and a casebook of local government birth promotion policies. The dependent variable was fertility rate, and the independent variable was fertility promotion policy. Using SPSS 25.0 and M-plus 8.0 programs, descriptive statistical analysis and latent growth modeling were conducted. An unconditional quadratic function change model was selected as a final model of this study.

Results

The average of the initial fertility rate and the linear rate of change in the Korean fertility rate, and the rate of change of the quadratic function were all statistically significant, meaning that the fertility rate of decline increases over time. Also, the linear rate of change and the quadratic function change rate were significant, showing significant differences in the initial level and rate of change of the fertility rate between local governments. Among fertility policies, only the in-kind policy had a significant effect on the initial value of the fertility rate, meaning that the higher the number of in-kind policies, the higher the fertility rate.

Conclusion

This study is crucial as it examined the changes in the fertility rate of Korean local governments as well as the policy factors affecting the fertility rate at a quantitative level.
Impact of COVID-19-related care disruptions on blood pressure management and control in community health centers
Authors: Meador Margaret , Coronado Fátima , Roy Debosree , Bay R. Curtis , Lewis Joy H. , Chen Jessica , Cheung Rachel , Utman Christopher , Hannan Judith A.
Published: December 2022

Background

Uncontrolled hypertension is a leading risk factor for cardiovascular disease. To ensure continuity of care, community health centers (CHCs) nationwide implemented virtual care (telehealth) during the pandemic. CHCs use the Centers for Medicare & Medicaid Services (CMS) 165v8 Controlling High Blood Pressure measure to report blood pressure (BP) control performance. CMS 165v8 specifications state that if no BP is documented during the measurement period, the patient’s BP is assumed uncontrolled.

Methods

To examine trends in BP documentation and control rates in CHCs as telehealth use increased during the pandemic compared with pre-pandemic period, we assessed documentation of BP measurement and BP control rates from December 2019 - October 2021 among persons ages 18-85 with a diagnosis of hypertension who had an in-person or telehealth encounter in 11 CHCs. Rates were compared between CHCs that did and did not implement self-measured BP monitoring (SMBP).

Results

The percent of patients with hypertension with no documented BP measurement was 0.5% in December 2019 and increased to 15.2% (overall), 25.6% (non-SMBP CHCs), and 11.2% (SMBP CHCs) by October 2021. BP control using CMS 165v8 was 63.5% in December 2019 and decreased to 54.9% (overall), 49.1% (non-SMBP), and 57.2% (SMBP) by October 2021. When assessing BP control only in patients with documented BP measurements, CHCs largely maintained BP control rates (63.8% in December 2019; 64.8% (overall), 66.0% (non-SMBP), and 64.4% (SMBP) by October 2021).

Conclusions

The transition away from in-person to telehealth visits during the pandemic likely increased the number of patients with hypertension lacking a documented BP measurement, subsequently negatively impacting BP control using CMS 165v8. There is an urgent need to enhance the flexibility of virtual care, improve EHR data capture capabilities for patient-generated data, and implement expanded policy and systems-level changes for SMBP, an evidence-based strategy that can build patient trust, increase healthcare engagement, and improve hypertension outcomes.
Hooked embracing plate for Rolando fracture fixation: a preliminary result
Authors: Tsai Yueh-Ju , Yeh Jui-Po , Lin Tsen-Hung , Lin Tsan-Shiun , Hsieh Ching-Hua
Published: December 2022

Background

Rolando fracture is a comminuted, intra-articular fracture over the metacarpal bone base of the thumb which often leads to joint instability and requirement of surgery. The aim of this study is to evaluate the radiological and functional outcomes of Rolando fracture following surgical fixation with a hooked embracing plate (Acumed, 1.3 mm, Rolando Fracture Hooked Plate) designed for Rolando fracture.

Method

We retrospectively reviewed a consequence of patients between 2018 and 2022 with Rolando fracture who received open reduction internal fixation with hooked embracing plates. Primary endpoints were the quality of radiologic reduction after the operation and peri-operative complications. Secondary outcomes were bone union, pinch and grip strength, palmar abduction, opposition and radiographic osteoarthritis over the trapeziometacarpal (TMC) joint.

Results

A total of 5 patients were included. All patients had good quality of radiological reduction without peri-operative complications. The opposition, abduction, pinch and grip strength were nearly full-recovered for all patients with fine bone unions after 3 months follow-up.

Conclusion

The hooked embracing plate is a good and safe option for surgical fixation in patients with Rolando fracture. Compared with traditional method such as lag screw or mini-plate fixation, the hooked embracing plate could provide rigid fixation with fine radiologic and functional outcomes with early mobilization.
Mapping the evidence for monitoring fluoride exposure in community prevention programmes for oral health using nail clippings and spot urine samples: a scoping review
Authors: Kumah Elizabeth Adjoa , Eskandari Fatemeh , Azevedo Liane B. , John Sherley , Zohoori Fatemeh Vida
Published: December 2022

Background

There is an increased interest in identifying practical and accurate biomarkers for fluoride exposure. Due to the narrow ‘dose-gap’ between the benefit of caries reduction and the risk of dental fluorosis, monitoring of fluoride exposure is vital when introducing any fluoridation programme for the prevention of dental caries. This scoping review aimed to ascertain the nature and extent of the available evidence on how spot urine and nail clippings are used to measure fluoride intake/exposure, by using a unique approach of mapping the studies according to population, setting, type of study design, methodology and analytical approach in community prevention programmes.

Methods

Multiple relevant databases were searched up to July 2021 for any study designs, including randomised controlled studies, quasi-experimental studies, surveys, retrospective and prospective cohort studies, case studies, phenomenological studies, and expert opinions.

Results

The search retrieved 9,222 studies of which 155 met the inclusion criteria. A high proportion of the studies (25.2%) originated from Latin America and the Caribbean continent subregion. However, per country, China recorded the highest number, followed by India and Mexico. The majority (62.6%) employed a cross-sectional study design, and 65.8% combined participants from different age groups. Of the included studies, 82.6% used spot urine samples as a biomarker for assessing fluoride intake/exposure. Water fluoride concentration was reported in 66.5% of the studies with 46.6% of all included studies reporting a water fluoride concentration of > 1.2 mg/L. The methods used in assessing oral hygiene and dietary intake were not reported in 72.3% and 71.0% of the included studies, respectively. Only 35.5% of the included studies assessed the relationship between fluoride exposure and excretion.

Conclusions

This review revealed a large variability in the way in which spot urine samples and/or nail clippings are used to measure fluoride exposure in different settings and situations. Particularly, there are inconsistencies in the methodologies and the analytical approaches used in assessing fluoride exposure. Therefore, there is a need for more rigorous primary research studies using standardised approaches to determine the suitability of spot urine samples and nail clipping as biomarkers for monitoring fluoride exposure.
Effects of exercise on inflammatory factors and IGF system in breast cancer survivors: a meta-analysis
Authors: Zhou Yanan , Jia Ningxin , Ding Meng , Yuan Kai
Published: December 2022

Background

At present, there are multiple hypotheses regarding the mechanisms underlying the effect of exercise on the postoperative inflammatory factors and the IGF system among breast cancer patients, especially. To determine the underlying mechanisms, prevent the recurrence of breast cancer and improve its prognosis, this paper will systematically evaluate the impact of exercise on inflammatory factors and the IGF system in breast cancer survivors.

Methods

The PubMed, Embase, Web of Science, CNKI, Wanfang and VIP (Chinese scientific and technical journals) databases were systematically searched until April 2021. The search terms included 'exercise', 'inflammatory factor', 'IGF system' and 'breast cancer'. A total of 1066 relevant articles were retrieved. The articles were screened according to inclusion and exclusion criteria, such as study population, intervention method and type of experiment, and 11 articles were ultimately included. All statistical results were analysed using STATA 14.0 and Rstudio 4.1.1.

Results

We found that exercise significantly reduced the level of IGF-1 (WMD, -19.947 ng/ml; 95% CI, -22.669 to -17.225; P = 0.000). Subgroup analysis showed that in the studies with an intervention period > 12 weeks, exercise significantly reduced IL-6 levels (WMD, -0.761 pg/ml; 95% CI, -1.369 to -0.153; p = 0.014), while in the studies with an intervention period ≤ 12 weeks, exercise significantly reduced CRP (WMD, -2.381 mg/L; 95% CI, -4.835 to 0.073, P = 0.001) and IL-10 levels (WMD, -7.141 pg/ml, 95% CI, -10.853 to -3.428; P = 0.000). In addition, aerobic exercise plus resistance training significantly reduced IL-6 levels (WMD, -1.474 pg/ml; 95% CI, -1.653 to -1.296; P = 0.000). The results of the sensitivity analysis showed that after excluding the studies with high heterogeneity, exercise significantly reduced the TNF-α levels in patients with breast cancer (WMD, -1.399 pg/ml; 95% CI, -1.718 to -1.080; P = 0.000).

Conclusion

Exercise reduces the postoperative levels of IGF-1, IL-6, CRP, IL-10 and TNF-α among patients with breast cancer, which may have a significant impact on inhibiting breast cancer recurrence and improving its prognosis. Future studies should examine the effects of different durations and types of exercise to develop individualized exercise prescriptions for breast cancer patients.
Determining the readiness of patients with renal failure to use health information technology
Authors: Tabas Raana Younesi , Ahmadian Leila , Samadbeik Mahnaz , Arian Anahita , Ameri Arefeh
Published: December 2022

Introduction

Using information technology (IT) for purposes such as patient education and disease prevention and management is effective when patients are ready to use it. The objective of this study was to determine the readiness of patients with renal failure to use health IT.

Methods

This study was performed on all dialysis patients in South Khorasan province (n = 263) using a 28-item questionnaire. The questionnaire consisted of (1) demographic information of participants and (2) questions concerning eight main factors including the need for information, desire to receive information, ability to use computers and the Internet, computers and the Internet anxiety, communication with physicians, using mobile phones and concerns about security and confidentiality of information. Descriptive statistics and Mann–Whitney and Kruskal–Wallis statistical tests were used to analyze the data.

Results

About 15% of the participants stated that they do not want to receive information from the Internet. Anxiety and concern about Internet security and confidentiality were higher in women, married people, people over 60, villagers, and illiterate people (p < 0.05). Married people and people over 60 years had a higher desire to get information (p < 0.05). The rate of computer anxiety and Internet privacy concern was higher than average (p < 0.001). Most patients (34.2%) could only send text messages using mobile phones.

Conclusion

Despite the need of most patients to online health information, they do not use this information due to a lack of skills and experience to use IT. Therefore, the ability of users should be considered when developing IT-based interventions. Due to patients' concerns about Internet privacy, it is required to teach patients how to protect their privacy while using the Internet.
Economic hardship among principal family caregivers of cancer patients at Khartoum oncology hospital 2020: a cross-sectional study
Authors: Elgadi Ammar , Hisham Aseel , Ahmed Hayat A. , Elzaki Hiba Ali , shaaban Kamil Merghani Ali , Dafaalla Ola , Elkhidir Osama Ahmed , Alrawa Salma S. , Mahmoud Tahani Amin , Wadidi Waad
Published: December 2022

Background

The impact of cancer extends beyond patients and consumes their families. Family members are widely recognized as informal caregivers. The economic burden on family caregivers is increased with new treatments, prolonged survival, and reduced stay in the acute care setting. This is especially true in African countries where family bonds are sacred and health system is fragile that they need to pay out of pocket for care.

The aim of this study is to estimate the perceived caregivers’ economic burden in the subsequent aspects: financial strain, inability to make ends meet, not enough money for necessities, and economic adjustments/cutbacks.

Method

This study was a quantitative, descriptive cross-sectional study conducted at Khartoum oncology hospital. Included 143 caregivers of cancer patients. Data were collected through face-to-face interviews using the socio-demographic Questionnaire and Economic Hardship Questionnaire (EHQ).

Results

One hundred forty-three cancer patients and their caregivers were included. 56.6% of patients were females, and about 32.2% were aged 51–65 years. The most common cancer types were breast cancer and leukemia. Roughly 33% of patients had stage IV cancer on presentation, and about 53.9% received chemotherapy. Unlike cancer patients, (47.6%) of family caregivers were aged 18–34 years, yet they were mainly females (54.4%). Most of them (34.3%) were unemployed, with a mean monthly gross income of 53.3 dollars, while the mean household monthly gross income was 113.0 dollars. The mean score of the economic hardship scale was 35.8 out of 64. Most of the caregivers experience no difficulties affording necessities. However, they experience difficulties with medical and leisure activities.

There was no significant association between caregiver economic hardship and cancer patient characteristics (patients' age, cancer stage, and treatment type). However, there was a significant association between caregivers' economic hardships and their gender, marital status, educational level, occupation, caregiver monthly gross income, and household monthly gross income.

Conclusion

The study findings suggest a moderate financial burden among cancer caregivers. The predicting factors include being single, a student, male, of higher educational level, and lower income. Financial difficulties are associated with maladaptive behavior and should come to light.
A multi-center, single-arm, phase II study of anlotinib plus paclitaxel and cisplatin as the first-line therapy of recurrent/advanced esophageal squamous cell carcinoma
Authors: Li Ning , Wu Tao , Hong Yong-Gui , Guo Yan-Zhen , Cheng Yu-Feng , Ma Yi-Jie , Bie Liang-Yu , Cui Dong-Hai , Gao Xiao-Hui , Tan Bing-Xu , Li Bao-Sheng , Luo Su-Xia , Wang Jun-Sheng
Published: December 2022

Background

Anlotinib, a tyrosine kinase inhibitor, has shown encouraging anti-tumor activity in esophageal squamous cell carcinoma (ESCC). This study was designed to assess the efficacy and safety of anlotinib plus paclitaxel and cisplatin (TP) as first-line therapy for advanced ESCC.

Methods

In a multi-center, single-arm, phase II clinical trial, patients (aged > 18 years) with ESCC, which was judged to be locally advanced, recurrent, or metastatic, received 10 mg oral anlotinib once daily on days 1–14, 135 mg/m2 intravenous paclitaxel on day 1, and 60–75 mg/m2 intravenous cisplatin on days 1–3 every 3 weeks for a maximum of 4–6 cycles as the initial therapy in five centers in China. Subsequently, patients received anlotinib monotherapy (10 mg) as maintenance therapy until tumor progression or intolerable toxicity. The primary endpoint was progression-free survival (PFS).

Results

Forty-seven patients were enrolled in this study between October 2019 and March 2021. The median follow-up was 14.04 months (IQR, 9.30–19.38). Of 46 with assessable efficacy, the median PFS and median overall survival were 8.38 months (95% CI, 6.59–10.17) and 18.53 months (95% CI, 13.11–23.95), respectively. The objective response rate was 76.1% (95% CI, 61.2–87.4%), with 4 (8.7%) complete responses and 31 (67.4%) partial responses. The disease control rate was 91.3% (95% CI, 79.2–97.6%). The median duration of response was 6.80 months (95% CI, 4.52–9.08), and 1 patient had an ongoing response for 23 months. Subgroup analysis revealed no association between clinical factors and survival or response. Of the 47 patients with assessable safety, the main grade ≥ 3 treatment-emergent adverse events (TEAEs) were neutropenia (17.0%), bone marrow suppression (12.8%), and vomiting (10.6%). No treatment-related deaths or serious TEAEs were observed. Notably, higher c-Kit levels were an independent factor for superior PFS (HR = 0.032; 95% CI, 0.002–0.606; P = 0.022).

Conclusions

The study demonstrated a manageable safety profile and durable clinical response of anlotinib plus TP as first-line therapy in advanced ESCC, which suggested a potential therapeutic option for this population.

Trial registration

ClinicalTrials.gov NCT04063683. Registered 21 August 2019.
Tumor PKCδ instigates immune exclusion in EGFR-mutated non–small cell lung cancer
Authors: Zuo Yi-Han , Gao Wei-Na , Xie Ya-Jia , Yang Sheng-Yong , Zhou Jin-Tai , Liang Hai-Hai , Fan Xing-Xing
Published: December 2022

Background

The recruitment of a sufficient number of immune cells to induce an inflamed tumor microenvironment (TME) is a prerequisite for effective response to cancer immunotherapy. The immunological phenotypes in the TME of EGFR–mutated lung cancer were characterized as non-inflamed, for which immunotherapy is largely ineffective.

Methods

Global proteomic and phosphoproteomic data from lung cancer tissues were analyzed aiming to map proteins related to non-inflamed TME. The ex vivo and in vivo studies were carried out to evaluate the anti-tumor effect. Proteomics was applied to identify the potential target and signaling pathways. CRISPR-Cas9 was used to knock out target genes. The changes of immune cells were monitored by flow cytometry. The correlation between PKCδ and PD-L1 was verified by clinical samples.

Results

We proposed that PKCδ, a gatekeeper of immune homeostasis with kinase activity, is responsible for the un-inflamed phenotype in EGFR-mutated lung tumors. It promotes tumor progression by stimulating extracellular matrix (ECM) and PD-L1 expression which leads to immune exclusion and assists cancer cell escape from T cell surveillance. Ablation of PKCδ enhances the intratumoral penetration of T cells and suppresses the growth of tumors. Furthermore, blocking PKCδ significantly sensitizes the tumor to immune checkpoint blockade (ICB) therapy (αPD-1) in vitro and in vivo model.

Conclusions

These findings revealed that PKCδ is a critical switch to induce inflamed tumors and consequently enhances the efficacy of ICB therapy in EGFR-mutated lung cancer. This opens a new avenue for applying immunotherapy against recalcitrant tumors.

Graphical Abstract
Frailty and risk of microvascular complications in patients with type 2 diabetes: a population-based cohort study
Authors: Wu Yuanjue , Xiong Ting , Tan Xiao , Chen Liangkai
Published: December 2022

Background

Cross-sectional studies found that frailty was associated with prevalent diabetic microvascular complications (DMC). Longitudinal evidence in this regard is inconclusive and insufficient. We aimed to prospectively evaluate the association of pre-frailty and frailty with DMC in patients with type 2 diabetes (T2D).

Methods

We included 18,062 adults (mean age 59.4 ± 7.2 years, 37.4% female) with T2D at baseline in the UK Biobank. Frailty was defined using the frailty phenotype according to five components (weight loss, exhaustion, low physical activity, slow gait speed, and low grip strength). DMC, defined as diabetic nephropathy, diabetic neuropathy, or diabetic retinopathy, was identified using hospital inpatient records and death registries. Cox proportional hazard regression models considering competing risks were used to evaluate the associations of frailty phenotype with overall DMC events and subtypes.

Results

Among all participants, 6101 (33.8%) were classified as non-frail, 10,073 (55.8%) were classified as pre-frail, and 1888 (10.4%) were classified as frail. During a median follow-up of 12.0 years, 3678 DMC cases were documented, including 2213 diabetic nephropathy, 1520 diabetic retinopathy, and 673 diabetic neuropathy events. In the multivariable-adjusted model, compared with participants with non-frail, both pre-frailty and frailty were significantly associated with increased risk of overall DMC (HR 1.10, 95% CI: [1.02, 1.18] for pre-frailty and HR 1.52 [95% CI: 1.36, 1.69] for frailty). Similar results were observed in the subtypes of DMC. For each one-point increase in frailty phenotype score, the risk of overall DMC, diabetic nephropathy, diabetic retinopathy, and diabetic neuropathy event increased by 13%, 16%, 10%, and 20%, respectively.

Conclusions

Both pre-frailty and frailty were associated with an increased risk of DMC in patients with T2D. These findings have important implications for integrating early assessment and surveillance of frailty in diabetes and may favor the identification of at-risk patients.
Time series evaluation of condemnation at poultry slaughterhouses enable to export in Southeastern Brazil (2009–2019): a tool for optimizing resources in the poultry production chain
Authors: Hortêncio Maria Carolina , Costa Letícia Roberta Martins , de Souza Maria Victória Pereira , de Freitas Weslley Domenicci , Fonseca Belchiolina Beatriz , Silva Marcelo José Barbosa , Cossi Marcus Vinícius Coutinho
Published: December 2022

Background

Even with the technological advances in management, health and genetics applied to poultry farming worldwide, there is still a high rate of carcasses condemnation at slaughterhouses, which result in losses for the poultry production chain. Thus, this work aimed to evaluate the condemnation occurrence index (COI) and adjusted seasonal index (ASI) of poultry (turkey, griller, and heavy chicken) between 2009 and 2019, in a slaughterhouse enable to export in southeastern Brazil. Data were obtained from official spreadsheets from the Brazilian Federal Inspection Service (FIS) and used to calculate the COI, correlation analysis between the main causes of condemnation, and ASI assessments throughout the year.

Results

Seven percent (55,594,318) of the poultry carcasses were condemned (partial or total), and the most frequent causes, contamination, and contusion/traumatic injury, amounted to 63.5% of the total condemnation. There was a trend of increasing condemnation throughout the time series evaluated, with COI varying between 45,282–149,809 condemnations per 1,000,000 poultry slaughtered. Considering the ASI, it was identified that for ascitic syndrome, July has a higher index value (1.63) than the months between January–June (P < 0.05).

Conclusions

The main causes of condemnation were contamination and contusion/traumatic injury, both technological causes. ASI showed that in July there is a greater carcasses condemnation due to ascitic syndrome than in the months between January and June. The variations observed in the ASIs can provide subsidies for preventive measures and optimization of human and financial resources, generating positive impacts on food safety, productivity, and profitability of the sector.
Abnormal pulmonary hemodynamics during exercise is associated with exercise capacity in COPD
Authors: Sassmann Teresa , Douschan Philipp , Foris Vasile , Tröster Natascha , Zeder Katarina , Brcic Luka , Tornyos Adrienn , Bachmaier Gerhard , Fuchsjäger Michael , Olschewski Horst , Kovacs Gabor
Published: December 2022

Background

Pulmonary hypertension (PH) is a frequent complication in COPD and it is associated with decreased exercise capacity and poor prognosis. We hypothesized that even in COPD patients without significant PH at rest, abnormal pulmonary hemodynamics during exercise affect exercise capacity.

Methods

Consecutive COPD patients with clinically indicated right heart catheterization and resting mean pulmonary arterial pressure (mPAP) < 25 mmHg and age- and sex-matched controls with the same limits of pulmonary hemodynamics but no chronic lung disease who underwent clinical work-up including invasive hemodynamic assessment during exercise, were retrospectively analyzed. Chi-square tests were used to evaluate differences between groups for categorical data and Fisher’s exact test or Mann–Whitney-U-tests for continuous variables. Associations were analyzed with Spearman rank correlation tests.

Results

We included n = 26 COPD patients (female/male: 16/10, 66 ± 11 yr, FEV1: 56 ± 25%predicted) and n = 26 matched controls (FEV1: 96 ± 22%predicted). At rest, COPD patients presented with slightly increased mPAP (21 (18–23) vs. 17 (14–20) mmHg, p = 0.022), and pulmonary vascular resistance (PVR) [2.5 (1.9–3.0) vs. 1.9 (1.5–2.4) WU, p = 0.020] as compared to controls. During exercise, COPD patients reached significantly higher mPAP [47 (40–52) vs. 38 (32–44) mmHg, p = 0.015] and PVR [3.1 (2.2–3.7) vs. 1.7 (1.1–2.9) WU, p = 0.028] values despite lower peak exercise level [50 (50–75) vs. 100 (75–125) Watt, p = 0.002]. The mPAP/cardiac output slope was increased in COPD vs. controls [6.9 (5.5–10.9) vs. 3.7 (2.4–7.4) mmHg/L/min, p = 0.007] and negatively correlated with both peak oxygen uptake (r = − 0.46, p = 0.007) and 6-min walk distance (r = − 0.46, p = 0.001).

Conclusion

Even in the absence of significant PH at rest, COPD patients reveal characteristic abnormalities in pulmonary hemodynamics during exercise, which may represent an important exercise-limiting factor.
Exosomal LINC00460/miR-503-5p/ANLN positive feedback loop aggravates pancreatic cancer progression through regulating T cell–mediated cytotoxicity and PD-1 checkpoint
Authors: Yao Jun , Gao Ruoyu , Luo Minghan , Li Defeng , Guo Liliangzi , Yu Zichao , Xiong Feng , Wei Cheng , Wu Benhua , Xu Zhenglei , Zhang Dingguo , Wang Jianyao , Wang Lisheng
Published: December 2022

Background

Long non-coding RNA (lncRNA) LINC00460 is an onco-lncRNA in a variety of cancers, including pancreatic cancer (PC). This study is aimed to investigate the regulatory mechanisms of LINC00460 in PC.

Methods

The tumor and adjacent normal tissues were collected from 73 PC patients. The expression of LINC00460, miR-503-5p, and ANLN was detected using qRT-PCR. We then analyzed the proliferation, migration, invasion, and apoptosis/cell cycle of PC cells by performing the MTT/EdU, transwell, and flow cytometry assays, respectively. The xenograft tumor model were utilized to confirm the effect of LINC00460 knockdown on PC through anti-PD-1 therapy in vivo, and the sensitivity of PANC-1 cells to the cytotoxicity of CD8+ T cells in vitro. Western blotting was used to determine the protein levels. A co-culture model was utilized to explore the effects of exosomes on macrophages.

Results

LINC00460 was up-regulated in PC tissues and cells. LINC00460 knockdown suppressed cell proliferation, migration, and invasion, facilitated cell apoptosis and G0/G1 phase arrest, and inhibited the tumor growth through anti-PD-1 therapy. Both miR-503-5p down-regulation and ANLN up-regulation reversed the effects of LINC00460 knockdown on inhibiting the proliferation, migration and invasion, and on promoting the apoptosis, G0/G1 phase arrest, and the sensitivity of PC cells to the cytotoxicity of CD8+ T cells. Exosomes were uptaken by the ambient PC cells. PANC-1 cells-derived exosomal LINC00460-induced M2 macrophage polarization accelerates the cell migration and invasion.

Conclusions

LINC00460 silencing attenuates the development of PC by regulating the miR-503-5p/ANLN axis and exosomal LINC00460-induced M2 macrophage polarization accelerates the migration and invasion of PANC-1 cells, thus LINC00460 may act as a possible therapeutic target for treating PC.
Triglyceride-glucose index level and variability and outcomes in patients with acute coronary syndrome undergoing percutaneous coronary intervention: an observational cohort study
Authors: Wang Yue , Wang Yue , Sun Shuaifeng , Liu Xinyan , Zhao Wenxin , Li Wenzheng , Suo Min , Wu Zheng , Wu Xiaofan
Published: December 2022

Background

The associations between the long-term triglyceride-glucose (TyG) index level and variability and clinical outcomes in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) have not been well studied.

Methods

A total of 1,694 ACS patients with at least three postbaseline TyG index measurements within 2 years after PCI were included in the present study. The TyG index was defined as ln (fasting triglycerides [mg/dL] × fasting plasma glucose [mg/dL]/2). Multivariable-adjusted Cox proportional hazard models were used to examine the association between baseline and mean TyG index levels and TyG index variability and the risk of major adverse cardiovascular and cerebrovascular events (MACCEs).

Results

During the median follow-up of 31 months, the overall incidence of MACCE was 5.9%. Both high baseline and mean TyG index levels were independently associated with an increased risk of MACCEs after adjustment for multiple potential confounders (hazard ratio [HR) 1.76 95% confidence interval [CI] 1.06–2.93; and HR 2.73 95% CI 1.57–4.74). Similarly, higher TyG index variability by successive variation (SD) was well related to a higher prevalence of MACCEs (HR 2.17 95% CI 1.28–3.68). In addition, the mean TyG index level showed a stronger risk prediction for MACCEs than the baseline TyG index level and TyG index-SD (AUCs 0.618 vs 0.566 vs 0.566).

Conclusions

The risk of MACCEs significantly increased with higher baseline and mean TyG index levels, as well as TyG index variability, in patients with ACS undergoing PCI. In particular, the mean TyG index level exhibited the highest predicting ability for MACCEs. Therefore, monitoring the long-term pattern of the TyG index deserves attention in clinical practice.
Chronic exposure to the star polycation (SPc) nanocarrier in the larval stage adversely impairs life history traits in Drosophila melanogaster
Authors: Yan Shuo , Li Na , Guo Yuankang , Chen Yao , Ji Chendong , Yin Meizhen , Shen Jie , Zhang Junzheng
Published: December 2022

Background

Nanomaterials are widely used as pesticide adjuvants to increase pesticide efficiency and minimize environmental pollution. But it is increasingly recognized that nanocarrier is a double-edged sword, as nanoparticles are emerging as new environmental pollutants. This study aimed to determine the biotoxicity of a widely applied star polycation (SPc) nanocarrier using Drosophila melanogaster, the fruit fly, as an in vivo model.

Results

The lethal concentration 50 (LC50) value of SPc was identified as 2.14 g/L toward third-instar larvae and 26.33 g/L for adults. Chronic exposure to a sub lethal concentration of SPc (1 g/L) in the larval stage showed long-lasting adverse effects on key life history traits. Exposure to SPc at larval stage adversely impacted the lifespan, fertility, climbing ability as well as stresses resistance of emerged adults. RNA-sequencing analysis found that SPc resulted in aberrant expression of genes involved in metabolism, innate immunity, stress response and hormone production in the larvae. Orally administrated SPc nanoparticles were mainly accumulated in intestine cells, while systemic responses were observed.

Conclusions

These findings indicate that SPc nanoparticles are hazardous to fruit flies at multiple levels, which could help us to develop guidelines for further large-scale application.
Effect of Coenzyme Q10 and transcutaneous electrical acupoint stimulation in assisted reproductive technology: a retrospective controlled study
Authors: Qi Shanqin , Liang Qi , Yang Lixia , Zhou Xueyuan , Chen Kun , Wen Ji
Published: December 2022

Purpose

To investigate the effects of coenzyme Q10 (CoQ10) and transcutaneous electrical acupoint stimulation (TEAS) pretreatment on pregnancy in patients with poor ovarian response (POR).

Methods

A total of 330 POR patients who were pretreated with CoQ10 or CoQ10 combined with TEAS before their in vitro fertilization/intracytoplasmic sperm injection and embryo transfer (IVF/ICSI-ET) cycles and who were not pretreated were selected and divided into CoQ10 group (group A, n = 110), CoQ10 + TEAS group (group B, n = 110) and control group (group C, n = 110). For patients with 2 or more transfer cycles, only the information of the first cycle was included. Ovarian function, response to gonadotropin (Gn) stimulation, and pregnancy outcomes of the three groups were compared in the IVF/ICSI-ET cycles.

Results

After pretreatment, basal FSH, total Gn dosage and duration were comparable among the three groups (all p-value > 0.05), basal E2 in group B decreased significantly compared with the control group (p = 0.022). Endometrial thickness on the human chorionic gonadotropin (hCG) day, antral follicle counts (AFC), the numbers of oocytes, metaphase II (MII) eggs and excellent embryos in the two pretreatment groups were significantly increased compared with group C (all p-value < 0.001), but the rates of MII oocytes, fertilization and excellent embryos had no apparent change. The endometrial thickness on the day of hCG, the numbers of MII eggs and excellent embryos in group B were higher than those in group A (p < 0.001; p = 0.020; p = 0.027; respectively). The embryo implantation rate (IR), clinical pregnancy rate (CPR) and live birth rate (LBR) in group B were significantly higher than those in group C (p = 0.022; p = 0.010; p = 0.019; respectively), but not significantly different from group A.

Conclusion

CoQ10 alone or in combination with TEAS are effective methods for IVF/ICSI-ET adjuvant therapy, which can significantly improve ovarian reactivity, increase the numbers of retrieved eggs and superior embryos, and improve endometrial receptivity. Adjuvant TEAS on the basis of CoQ10 can significantly enhance pregnancy rates, but CoQ10 alone failed to present such an obvious effect.
Can successful pregnancy be achieved and predicted from patients with identified ZP mutations? A literature review
Authors: Zhou Juepu , Wang Meng , Yang Qiyu , Li Dan , Li Zhou , Hu Juan , Jin Lei , Zhu Lixia
Published: December 2022

Background

In mammals, normal fertilization depends on the structural and functional integrity of the zona pellucida (ZP), which is an extracellular matrix surrounding oocytes. Mutations in ZP may affect oogenesis, fertilization and early embryonic development, which may cause female infertility.

Methods

A PubMed literature search using the keywords ‘zona pellucida’, ‘mutation’ and ‘variant’ limited to humans was performed, with the last research on June 30, 2022. The mutation types, clinical phenotypes and pregnancy outcomes were summarized and analyzed. The naive Bayes classifier was used to predict clinical pregnancy outcomes for patients with ZP mutations.

Results

A total of 29 publications were included in the final analysis. Sixty-nine mutations of the ZP genes were reported in 87 patients with different clinical phenotypes, including empty follicle syndrome (EFS), ZP-free oocytes (ZFO), ZP-thin oocytes (ZTO), degenerated and immature oocytes. The phenotypes of patients were influenced by the types and location of the mutations. The most common effects of ZP mutations are protein truncation and dysfunction. Three patients with ZP1 mutations, two with ZP2 mutations, and three with ZP4 mutations had successful pregnancies through Intracytoplasmic sperm injection (ICSI) from ZFO or ZTO. A prediction model of pregnancy outcome in patients with ZP mutation was constructed to assess the chance of pregnancy with the area under the curve (AUC) of 0.898. The normalized confusion matrix showed the true positive rate was 1.00 and the true negative rate was 0.38.

Conclusion

Phenotypes in patients with ZP mutations might be associated with mutation sites or the degree of protein dysfunction. Successful pregnancy outcomes could be achieved in some patients with identified ZP mutations. Clinical pregnancy prediction model based on ZP mutations and clinical characteristics will be helpful to precisely evaluate pregnancy chance and provide references and guidance for the clinical treatment of relevant patients.
Standard dosing of enoxaparin versus unfractionated heparin in critically ill patient with COVID-19: a multicenter propensity-score matched study
Authors: Al Sulaiman Khalid , Aljuhani Ohoud , Korayem Ghazwa B. , Hafiz Awatif , Alalawi Mai , Badreldin Hisham A. , Altebainawi Ali F. , Vishwakarma Ramesh , Alissa Abdulrahman , Alghamdi Albandari , Alenazi Abeer A. , Al Enazi Huda , Alanazi Shahad , Alhammad Abdullah , Alghamdi Jahad , AlFaifi Mashael , Al Sehli Faisal A. , Aldossari Maram A. , Alhubaishi Alaa A. , Al-Ali Anfal Y. , Al-Dorzi Hasan M.
Published: December 2022

Background

Thrombotic events are common in critically ill patients with COVID-19 and have been linked with COVID-19- induced hyperinflammatory state. In addition to anticoagulant effects, heparin and its derivatives have various anti-inflammatory and immunomodulatory properties that may affect patient outcomes. This study compared the effectiveness and safety of prophylactic standard-doses of enoxaparin and unfractionated heparin (UFH) in critically ill patients with COVID-19. 

Methods

A multicenter, retrospective cohort study included critically ill adult patients with COVID-19 admitted to the ICU between March 2020 and July 2021. Patients were categorized into two groups based on the type of pharmacological VTE thromboprophylaxis given in fixed doses (Enoxaparin 40 mg SQ every 24 hours versus UFH 5000 Units SQ every 8 hours) throughout their ICU stay. The primary endpoint was all cases of thrombosis. Other endpoints were considered secondary. Propensity score (PS) matching was used to match patients (1:1 ratio) between the two groups based on the predefined criteria. Multivariable logistic, Cox proportional hazards, and negative binomial regression analysis were used as appropriate. 

Results

A total of 306 patients were eligible based on the eligibility criteria; 130 patients were included after PS matching (1:1 ratio). Patients who received UFH compared to enoxaparin had higher all thrombosis events at crude analysis (18.3% vs. 4.6%; p-value = 0.02 as well in logistic regression analysis (OR: 4.10 (1.05, 15.93); p-value = 0.04). Although there were no significant differences in all bleeding cases and major bleeding between the two groups (OR: 0.40 (0.07, 2.29); p-value = 0.31 and OR: 1.10 (0.14, 8.56); p-value = 0.93, respectively); however, blood transfusion requirement was higher in the UFH group but did not reach statistical significance (OR: 2.98 (0.85, 10.39); p-value = 0.09). The 30-day and in-hospital mortality were similar between the two groups at Cox hazards regression analysis. In contrast, hospital LOS was longer in the UFH group; however, it did not reach the statistically significant difference (beta coefficient: 0.22; 95% CI: -0.03, 0.48; p-value = 0.09).

Conclusion

Prophylactic enoxaparin use in critically ill patients with COVID-19 may significantly reduce all thrombosis cases with similar bleeding risk compared to UFH.
Neuromedin U secreted by colorectal cancer cells promotes a tumour-supporting microenvironment
Authors: Przygodzka Patrycja , Soboska Kamila , Sochacka Ewelina , Pacholczyk Marcin , Braun Marcin , Kassassir Hassan , Papiewska-Pająk Izabela , Kielbik Michal , Boncela Joanna
Published: December 2022

Background

Neuromedin U (NMU) was identified as one of the hub genes closely related to colorectal cancer (CRC) progression and was recently shown to be a motility inducer in CRC cells. Its autocrine signalling through specific receptors increases cancer cell migration and invasiveness. Because of insufficient knowledge concerning NMU accessibility and action in the tumour microenvironment, its role in CRC remains poorly understood and its potential as a therapeutic target is still difficult to define.

Methods

NMU expression in CRC tissue was detected by IHC. Data from The Cancer Genome Atlas were used to analyse gene expression in CRC. mRNA and protein expression was detected by real-time PCR, immunoblotting or immunofluorescence staining and analysed using confocal microscopy or flow cytometry. Proteome Profiler was used to detect changes in the profiles of cytokines released by cells constituting tumour microenvironment after NMU treatment. NMU receptor activity was monitored by detecting ERK1/2 activation. Transwell cell migration, wound healing assay and microtube formation assay were used to evaluate the effects of NMU on the migration of cancer cells, human macrophages and endothelial cells.

Results

Our current study showed increased NMU levels in human CRC when compared to normal adjacent tissue. We detected a correlation between high NMUR1 expression and shorter overall survival of patients with CRC. We identified NMUR1 expression on macrophages, endothelial cells, platelets, and NMUR1 presence in platelet microparticles. We confirmed ERK1/2 activation by treatment of macrophages and endothelial cells with NMU, which induced pro-metastatic phenotypes of analysed cells and changed their secretome. Finally, we showed that NMU-stimulated macrophages increased the migratory potential of CRC cells.

Conclusions

We propose that NMU is involved in the modulation and promotion of the pro-metastatic tumour microenvironment in CRC through the activation of cancer cells and other tumour niche cells, macrophages and endothelial cells.