bluuebunny/crossref_metadata_2025 huggingface dataset:
Perioperative transcutaneous electrical acupoint stimulation (pTEAS) in pain management in major spinal surgery patients
Authors: Wu Xinyuan , Huang Jieling , Zhang Yuling , Chen Luying , Ji Yandong , Ma Wuhua , Li Yuhui
Published: November 2022

Background

Lumbar disc herniation is seen in 5–15% of patients with lumbar back pain and is the most common spine disorder demanding surgical correction. Spinal surgery is one of the most effective management for these patients. However, current surgical techniques still present complications such as chronic pain in 10–40% of all patients who underwent lumbar surgery, which has a significant impact on patients’ quality of life. Research studies have shown that transcutaneous electrical acupoint stimulation (TEAS) may reduce the cumulative dosage of intraoperative anesthetics as well as postoperative pain medications in these patients.

Objective

To investigate the effect of pTEAS on pain management and clinical outcome in major spinal surgery patients.

Methods

We conducted a prospective, randomized, double-blind study to verify the effect of pTEAS in improving pain management and clinical outcome after major spinal surgery. Patients (n = 90) who underwent posterior lumbar fusion surgery were randomized into two groups: pTEAS, (n = 45) and Control (n = 45). The pTEAS group received stimulation on acupoints Zusanli (ST.36), Sanyinjiao (SP.6), Taichong (LR.3), and Neiguan (PC.6). The Control group received the same electrode placement but with no electrical output. Postoperative pain scores, intraoperative outcome, perioperative hemodynamics, postoperative nausea and vomiting (PONV), and dizziness were recorded.

Results

Intraoperative outcomes of pTEAS group compared with Control: consumption of remifentanil was significantly lower (P < 0.05); heart rate was significantly lower at the end of the operation and after tracheal extubation (P < 0.05); and there was lesser blood loss (P < 0.05). Postoperative outcomes: lower pain visual analogue scale (VAS) score during the first two days after surgery (P < 0.05); and a significantly lower rate of PONV (on postoperative Day-5) and dizziness (on postoperative Day-1 and Day-5) (P < 0.05).

Conclusion

pTEAS could manage pain effectively and improve clinical outcomes. It could be used as a complementary technique for short-term pain management, especially in patients undergoing major surgeries.

Trial registration

ChiCTR1800014634, retrospectively registered on 25/01/2018. http://medresman.org/uc/projectsh/projectedit.aspx?proj=183
Combination of thoracic epidural analgesia with patient-controlled intravenous analgesia versus traditional thoracic epidural analgesia for postoperative analgesia and early recovery of laparotomy: a prospective single-centre, randomized controlled trial
Authors: Xu Wenwen , Li Youpei , Li Nanqi , Sun Yu , Wang Chao , An Ke
Published: November 2022

Background

Thoracic epidural analgesia (TEA) has always been the first choice for postoperative pain treatment, but associated complications and contraindications may limit its use. Our study put forward a new analgesic strategy that combines TEA with patient controlled intravenous analgesia (PCIA) to optimize TEA.

Methods

Patients undergoing laparotomy were enrolled in this prospective randomized study. Patients were randomized to one of two groups: TEA/PCIA group and TEA group. Patients in TEA/PCIA group received TEA in the day of surgery and the first postoperative day and PCIA continued to use until the third postoperative day. Patients in TEA group received TEA for three days postoperatively. Visual analogue scale (VSA) pain scores at rest and on movement at 6, 24,48,72 h after surgery were recorded. In addition, the incidence of inadequate analgesia, adverse events, time to first mobilization, time to pass first flatus, time of oral intake recovery, time of urinary catheter removal, postoperative length of hospital stay, cumulative opioid consumption, and the overall cost were compared between the two groups. We examined VAS pain scores using repeated measures analysis of variance; P < 0.05 was considered as statistically significant.

Results

Eighty-six patients were analysed (TEA/PCIA = 44, TEA = 42). The mean VAS pain scores at rest and on movement in TEA/PCIA group were lower than TEA group, with a significant difference on movement and 48 h postoperatively (P < 0.05). The time to first mobilization and pass first flatus were shorter in TEA/PCIA group (P < 0.05). Other measurement showed no statistically significant differences.

Conclusions

The combination of TEA with PCIA for patients undergoing laparotomy, can enhance postoperative pain control and facilitate early recovery without increasing the incidence of adverse effects and overall cost of hospitalization.

Trial registration

Chinese Clinical Trial Registry(www.chictr.org.cn), ChiCTR 1,800,020,308, 13 December 2018.
Circulation and seasonality of influenza viruses in different transmission zones in Africa
Authors: Belizaire Marie Roseline Darnycka , N’gattia Anderson Kouabenan , Wassonguema Bibata , Simaleko Marcel Mbeko , Nakoune Emmanuel , Rafaï Clotaire , Lô Baidy , Bolumar Francisco
Published: November 2022

Background

Influenza is responsible for more than 5 million severe cases and 290,000 to 650,000 deaths every year worldwide. Developing countries account for 99% of influenza deaths in children under 5 years of age. This paper aimed to determine the dynamics of influenza viruses in African transmission areas to identify regional seasonality for appropriate decision-making and the development of regional preparedness and response strategies.

Methods

We used data from the WHO FluMart website collected by National Influenza Centers for seven transmission periods (2013–2019). We calculated weekly proportions of positive influenza cases and determined transmission trends in African countries to determine the seasonality.

Results

From 2013 to 2019, influenza A(H1N1)pdm2009, A(H3N2), and A(H5N1) viruses, as well as influenza B Victoria and Yamagata lineages, circulated in African regions. Influenza A(H1N1)pdm2009 and A(H3N2) highly circulated in northern and southern Africa regions. Influenza activity followed annual and regional variations. In the tropical zone, from eastern to western via the middle regions, influenza activities were marked by the predominance of influenza A subtypes despite the circulation of B lineages. One season was identified for both the southern and northern regions of Africa. In the eastern zone, four influenza seasons were differentiated, and three were differentiated in the western zone.

Conclusion

Circulation dynamics determined five intense influenza activity zones in Africa. In the tropics, influenza virus circulation waves move from the east to the west, while alternative seasons have been identified in northern and southern temperate zones. Health authorities from countries with the same transmission zone, even in the absence of local data based on an established surveillance system, should implement concerted preparedness and control activities, such as vaccination.
Analysis of CT and MR imaging features of the brain in patients with hydrogen sulfide poisoning based on clinical symptom grading
Authors: Tang Daidi , Tian Ning , Cai Jianming , Ma Jinlin , Wang Tingting , Zhang Hongtao , Sheng Fugeng
Published: November 2022

Objective

To retrospectively analyze CT and MR imaging features of the brain in patients with hydrogen sulfide poisoning based on clinical symptom grading and to investigate their correlations with clinical symptoms and patients’ prognosis.

Methods

A retrospective analysis was performed of CT and MR imaging data of the brain in 40 patients with hydrogen sulfide poisoning in our hospital. There were four main imaging manifestations. Patients were clinically graded according to the central nervous system symptom scores of the Poisoning Severity Score (PSS) and staged according to the gas inhalation time segment. Based on clinical symptom grading, the frequencies and proportions of four imaging signs that occurred in each group were counted, their development trends were analyzed, and the correlations of imaging features with clinical grading and prognosis were calculated.

Results

Forty patients were divided into minor, moderate and severe clinical grades and classified into four stages. In patients with minor and moderate clinical grading, only one patient suffered from generalized brain edema at stage 1, with a good prognosis. Patients with severe clinical grade showed the highest probability of presenting with the four imaging signs. The imaging signs were correlated with the severe clinical grade and a poor prognosis (P = 0.000, R = 0.828; P = 0.000, R = 0.858).

Conclusion

In patients with the severe clinical grade, generalized brain edema and symmetrical hypodensity/abnormal signals in the bilateral basal ganglia and around the lateral ventricles were the main findings and were shown to persist. The presence of imaging signs can assist in the clinically effective evaluation of clinical symptom grade.
Letrozole-induced endometrial preparation improved the pregnancy outcomes after frozen blastocyst transfer compared to the natural cycle: a retrospective cohort study
Authors: Ezoe Kenji , Fukuda Junichiro , Takeshima Kazumi , Shinohara Kazunori , Kato Keiichi
Published: November 2022

Background

Letrozole treatment is considered an effective option in endometrial preparation for frozen embryo transfers in patients with ovulation disorders or irregular menstruation; however, the effectiveness of letrozole-induced endometrial preparation remains unclear in ovulatory patients. Furthermore, there is no comparative study reporting on pregnancy complications and congenital anomalies after frozen embryo transfers comparing natural and letrozole-assisted cycles. This study examined whether letrozole-induced endometrial preparation affected pregnancy outcomes, perinatal outcomes, and congenital anomalies after single vitrified-warmed blastocyst transfers (SVBTs) in ovulatory patients, as compared with the natural cycle.

Methods

This historic cohort study included only patients with unexplained infertility. Overall, 14,611 patients who underwent SVBTs between July 2015 and June 2020, comprising both natural and letrozole-assisted cycles, were included. Multiple covariates that impact outcomes were used for propensity score matching; 1,911 patients in the letrozole group were matched to 12,700 patients in the natural group, and the clinical records of 1,910 patients in each group were retrospectively analysed. Cycle characteristics, pregnancy outcomes (clinical pregnancy, ongoing pregnancy, and live birth), and incidence of pregnancy complications and congenital anomalies were statistically compared between the two groups.

Results

Multivariate logistic regression analysis showed that letrozole administration during SVBT cycles significantly improved the live birth rate (P = 0.0355). Gestational age, birth length, birth weight, and infant sex, as well as the incidence of pregnancy complications and birth defects, were statistically comparable between the two groups. Furthermore, multivariate logistic regression analysis revealed that the perinatal outcomes were not affected by letrozole-induced endometrial preparation.

Conclusions

Letrozole-induced endometrial preparation improved the live birth rate compared with the natural cycle, without adverse effects on perinatal outcomes and congenital anomalies after SVBTs. Therefore, letrozole-induced endometrial preparation might be a safe and more effective strategy, especially for patients with insufficient luteal function.
Association between decreased ipsilateral renal function and aggressive behavior in renal cell carcinoma
Authors: Han Jang Hee , Jeong Seung-hwan , Han Sanghun , Yuk Hyeong Dong , Ku Ja Hyeon , Kwak Cheol , Kim Hyeon Hoe , Jeong Chang Wook
Published: November 2022

Background

To assess prognostic value of pre-operative ipsilateral split renal function (SRF) on disease-free survival (DFS) and its association with aggressive pathological features in renal cell carcinoma (RCC) patients. 

Methods

We examined patients registered in SNUG-RCC-Nx who underwent partial or radical nephrectomy at Seoul National University Hospital between January 1, 2010 and December 31, 2020. Patients with the following criteria were excluded from the study. 1) non-kidney origin cancer or benign renal tumor, 2) no pre-operative Tc 99 m-DTPA renal scan, 3) single kidney status or previous partial or radical nephrectomy, and 4) bilateral renal mass. Finally, 1,078 patients were included.

Results

Among 1,078 patients, 899 (83.4%) showed maintained ipsilateral SRF on DTPA renal scan; 179 patients (16.6%) showed decreased SRF. The decreased SRF group showed significantly large tumor size (maintained vs. decreased SRF; 3.31 ± 2.15 vs. 6.85 ± 3.25,p < 0.001), high Fuhrman grade (grade 3–4) (41.7% vs. 55.6%,p < 0.001), and high T stage (T stage 3–4) (9.0% vs. 20.1%,p < 0.001). Pathological invasive features, including invasion of the renal capsule, perirenal fat, renal sinus fat, vein, and collecting duct system, were associated with low SRF of the ipsilateral kidney. Univariate Cox regression analysis identified higher SSIGN (The stage, size, grade, and necrosis) score and decreased ipsilateral SRF as significant risk factors, while multivariate analysis showed SSIGN (5–7) (hazard ratio [HR] 11.9,p < 0.001) and SSIGN (8–10) (HR 69.2,p < 0.001) were significantly associated with shortened DFS, while decreased ipsilateral SRF (HR 1.75,p = 0.065) showed borderline significance. Kaplan–Meier analysis showed that decreased ipsilateral SRF (< 45%) group had shorter DFS than the other group (median DFS: 90.3 months vs. not reached,p < 0.001).

Conclusions

Among unilateral RCC patients, those with low ipsilateral SRF showed poor prognosis with pathologically invasive features. Our novel approach may facilitate risk stratification in RCC patients, helping formulate a treatment strategy.
Examining the relationships between trust in providers and information, mistrust, and COVID-19 vaccine concerns, necessity, and intentions
Authors: Williamson Lillie D. , Tarfa Adati
Published: November 2022

To facilitate maximum uptake of the COVID-19 vaccine, the roles of medical trust and mistrust of healthcare professionals must be examined. Previous work suggests that trust and mistrust may have differential impacts on vaccination intention via vaccine necessity and concerns. Multigroup structural equation modeling was utilized to test whether vaccine necessity and concerns mediated the associations between trust in providers and health information, mistrust of providers, and willingness to get the COVID-19 vaccine. The model was found to be invariant across Black and White respondents. Trust in providers and trust in healthcare information exerted indirect effects on intentions through vaccine necessity, while mistrust of providers exerted indirect effects through vaccine concerns. Unlike previous work, the forms of trust did not influence vaccine concerns. The findings have implications for future communication efforts from healthcare professionals and health messengers.
Improving the sense of city belonging among migrant elderly following family from an elderly service perspective: a cross-sectional study
Authors: Chu Meijie , Lee Chun-Yang , Suona Lamu , Gao Min , Chen Tianmu , Zhang Shuoxun , Chiang Yi-Chen
Published: November 2022

Background

The migrant elderly following family (MEFF), who migrates to new community to reunite with families, may face challenges of city integration and belonging. This study aims to explore from an elderly service perspective how to improve the sense of city belonging for MEFFs with and without hypertension/diabetes conditions.

Methods

Data were derived from the 2017 China Migrants Dynamic Survey and China National Statistical Yearbooks in 2017. The study included 882 MEFFs with hypertension or diabetes and 1266 MEFFs without hypertension and diabetes. Hierarchical linear modeling was applied to analyze the effects of individual and provincial elderly services on sense of city belonging among the MEFF with and without hypertension/diabetes.

Results

The MEFFs with hypertension or diabetes exhibited a greater sense of city belonging when they were familiar with a wider range of health education topics (γ = 0.05, p = 0.033) and were in those provinces with a greater number of licensed doctors (γ = 0.39, p < 0.001) and hospitals (p = 0.042). For those MEFFs without hypertension or diabetes, social security cards (γ = 0.57, p < 0.001) and awareness of a wider range of health education topics (γ = 0.07, p = 0.018) may help to improve their sense of city belonging.

Conclusion

This study calls for strengthening the accessibility in inclusive elderly services, and minimizing or even eliminating the inequality in elderly services at the individual and provincial levels to increase sense of city belonging among the MEFFs. For the MEFFs with hypertension or diabetes, health managers should focus on improving health information dissemination and increasing the number of doctors per 1000 people as well as and the number of hospitals to enhance the sense of city belonging. Moreover, the government should strengthen social security and health education to facilitate the adaptation and integration of MEFFs without hypertension and diabetes into the host city.
Risk analysis of grade ≥ 2 radiation pneumonitis based on radiotherapy timeline in stage III/IV non-small cell lung cancer treated with volumetric modulated arc therapy: a retrospective study
Authors: Yang Songhua , Huang Shixiong , Ye Xu , Xiong Kun , Zeng Biao , Shi Yingrui
Published: November 2022

Background

Radiotherapy is an important treatment for patients with stage III/IV non-small cell lung cancer (NSCLC), and due to its high incidence of radiation pneumonitis, it is essential to identify high-risk people as early as possible. The present work investigates the value of the application of different phase data throughout the radiotherapy process in analyzing risk of grade ≥ 2 radiation pneumonitis in stage III/IV NSCLC. Furthermore, the phase data fusion was gradually performed with the radiotherapy timeline to develop a risk assessment model.

Methods

This study retrospectively collected data from 91 stage III/IV NSCLC cases treated with Volumetric modulated arc therapy (VMAT). Patient data were collected according to the radiotherapy timeline for four phases: clinical characteristics, radiomics features, radiation dosimetry parameters, and hematological indexes during treatment. Risk assessment models for single-phase and stepwise fusion phases were established according to logistic regression. In addition, a nomogram of the final fusion phase model and risk classification system was generated. Receiver operating characteristic (ROC), decision curve, and calibration curve analysis were conducted to internally validate the nomogram to analyze its discrimination.

Results

Smoking status, PTV and lung radiomics feature, lung and esophageal dosimetry parameters, and platelets at the third week of radiotherapy were independent risk factors for the four single-phase models. The ROC result analysis of the risk assessment models created by stepwise phase fusion were: (area under curve [AUC]: 0.67,95% confidence interval [CI]: 0.52–0.81), (AUC: 0.82,95%CI: 0.70–0.94), (AUC: 0.90,95%CI: 0.80–1.00), and (AUC:0.90,95%CI: 0.80–1.00), respectively. The nomogram based on the final fusion phase model was validated using calibration curve analysis and decision curve analysis, demonstrating good consistency and clinical utility. The nomogram-based risk classification system could correctly classify cases into three diverse risk groups: low-(ratio:3.6%; 0 < score < 135), intermediate-(ratio:30.7%, 135 < score < 160) and high-risk group (ratio:80.0%, score > 160).

Conclusions

In our study, the risk assessment model makes it easy for physicians to assess the risk of grade ≥ 2 radiation pneumonitis at various phases in the radiotherapy process, and the risk classification system and nomogram identify the patient’s risk level after completion of radiation therapy.
Videofluoroscopic swallow study training for radiologists-in-training: a survey of practice and training needs
Authors: Coman Leah M. , Cardell Elizabeth A. , Richards John A. , Mahon Amanda , Lawrie Melissa D. , Ware Robert S. , Weir Kelly A.
Published: November 2022

Background

There is a lack of formal, published videofluoroscopic swallow study (VFSS) training targeting radiologists, yet radiology senior medical officers and resident medical officers (i.e., radiologists-in-training, known in Australia as “registrars”) are expected to be involved in VFSS interpretation of anatomical anomalies and reporting. This study investigated whether VFSS training is delivered to registrars during their specialist radiology training, whether it is a perceived need and, if so, to determine the desired content for inclusion in a targeted training package.

Methods

A cross-sectional, mixed methods study design was used. An internet-based survey was circulated via convenience and snowball sampling to radiologists (both senior medical officers and registrars) and speech-language pathologists across Australia in October-November 2017. Surveys also were distributed to practitioners based in New Zealand and the United Kingdom, as they practised within similar health systems, and it was anticipated they may have similar VFSS training practices. The radiology survey contained 36 questions and the speech-language pathology survey contained 44 questions. Participants were asked the following: (1) Report their current VFSS radiology registrar training environment; (2) Advise whether radiology registrars need VFSS training; (3) Recommend the content, format, training intensity, and evaluation methods for an effective radiology registrar training package. Demographic data were analysed descriptively, and open-ended responses were analysed using qualitative content analysis.

Results

21 radiology senior medical officers and registrars and 150 speech-language pathologists predominantly based at Australian tertiary hospital settings completed the survey. Most respondents (90.6%) identified that VFSS training is needed for radiology registrars. Only one speech-language pathologist respondent reported that they deliver VFSS training for radiology registrars. Specific content and teaching modalities for a VFSS training package, including diagnosing anatomical anomalies associated with dysphagia were recommended.

Conclusion

While most of the radiologists and speech-language pathologists surveyed did not deliver VFSS training to radiology registrars, they identified that targeted training is needed to improve radiology registrars’ effectiveness and engagement in VFSS clinics. The training package content, format and evaluation methods recommended by participants will inform the development of a VFSS training package targeting radiology registrars to be piloted at an Australian tertiary hospital.
Depot buprenorphine as an opioid agonist therapy in New South Wales correctional centres: a costing model
Authors: Ling R. , White B. , Roberts J. , Cretikos M. , Howard M. V. , Haber P. S. , Lintzeris N. , Reeves P. , Dunlop A. J. , Searles A.
Published: November 2022

Background

In 2019 daily liquid methadone and sublingual buprenorphine-naloxone were primary opioid agonist treatments for correctional centres in New South Wales, Australia. However, both had significant potential for diversion to other patients, and their daily administration was resource intensive. An alternative treatment in the form of subcutaneous depot buprenorphine became a viable option following a safety trial in 2020 – the UNLOC-T study. Depot preparation demonstrated advantages over current treatments as more difficult to divert and requiring fewer administrations. This paper reports the results of economic modelling of staffing costs in medication administration comparing depot buprenorphine, methadone, and sublingual buprenorphine provision in UNLOC-T trial facilities.

Methods

The costing study adopted a micro-costing approach involving the synthesis of cost data from the UNLOC-T clinical trial as well as data collected from Justice Health and Forensic Mental Health Network records. Labour and materials data were collected during site observations and interviews. Costs were calculated from two payer perspectives: a) the New South Wales (state) government which funds custodial and health services; and b) the Australian Commonwealth government, which pays for medications. The analysis compared the monthly-per-patient cost for each of the three medications in trial-site facilities during July 2019. This was followed by simulation of depot buprenorphine implementation across the study population. Costs associated with medical assessment and reviews were excluded.

Results

The monthly-per-patient New South Wales government service costs of depot buprenorphine, methadone and sublingual buprenorphine were: $151, $379 and $1,529 respectively while Commonwealth government medication costs were $434, $80 and $525. The implementation simulation found that service costs of depot buprenorphine declined as patients transitioned from weekly to monthly administration. Costs of treatment using the other medications increased as patient numbers decreased alongside fixed costs. At 12 months, monthly-per-patient service costs for depot buprenorphine, methadone and sublingual buprenorphine—which would be completely phased out by month 13—were $92, $530 and $2,162 respectively.

Conclusions

Depot buprenorphine was consistently the least costly of the treatment options. Future modelling could allow for dynamic patient populations and downstream impacts for participants and the state health system.

Trial registration

ACTRN12618000942257. Registered 4 June 2018.
Polygenic risk score improves the accuracy of a clinical risk score for coronary artery disease
Authors: King Austin , Wu Lang , Deng Hong-Wen , Shen Hui , Wu Chong
Published: November 2022

Background

The value of polygenic risk scores (PRSs) towards improving guideline-recommended clinical risk models for coronary artery disease (CAD) prediction is controversial. Here we examine whether an integrated polygenic risk score improves the prediction of CAD beyond pooled cohort equations. 

Methods

An observation study of 291,305 unrelated White British UK Biobank participants enrolled from 2006 to 2010 was conducted. A case–control sample of 9499 prevalent CAD cases and an equal number of randomly selected controls was used for tuning and integrating of the polygenic risk scores. A separate cohort of 272,307 individuals (with follow-up to 2020) was used to examine the risk prediction performance of pooled cohort equations, integrated polygenic risk score, and PRS-enhanced pooled cohort equation for incident CAD cases. The performance of each model was analyzed by discrimination and risk reclassification using a 7.5% threshold.

Results

In the cohort of 272,307 individuals (mean age, 56.7 years) used to analyze predictive accuracy, there were 7036 incident CAD cases over a 12-year follow-up period. Model discrimination was tested for integrated polygenic risk score, pooled cohort equation, and PRS-enhanced pooled cohort equation with reported C-statistics of 0.640 (95% CI, 0.634–0.646), 0.718 (95% CI, 0.713–0.723), and 0.753 (95% CI, 0.748–0.758), respectively. Risk reclassification for the addition of the integrated polygenic risk score to the pooled cohort equation at a 7.5% risk threshold resulted in a net reclassification improvement of 0.117 (95% CI, 0.102 to 0.129) for cases and − 0.023 (95% CI, − 0.025 to − 0.022) for noncases [overall: 0.093 (95% CI, 0.08 to 0.104)]. For incident CAD cases, this represented 14.2% correctly reclassified to the higher-risk category and 2.6% incorrectly reclassified to the lower-risk category.

Conclusions

Addition of the integrated polygenic risk score for CAD to the pooled cohort questions improves the predictive accuracy for incident CAD and clinical risk classification in the White British from the UK Biobank. These findings suggest that an integrated polygenic risk score may enhance CAD risk prediction and screening in the White British population.
A novel homozygous mutation in TRAPPC9 gene causing autosomal recessive non-syndromic intellectual disability
Authors: Amin Mutaz , Vignal Cedric , Eltaraifee Esraa , Mohammed Inaam N. , Hamed Ahlam A. A. , Elseed Maha A. , Babai Arwa , Elbadi Iman , Mustafa Doua , Abubaker Rayan , Mustafa Mohamed , Drunat Severine , Elsayed Liena E. O. , Ahmed Ammar E. , Boespflug-Tanguy Odile , Dorboz Imen
Published: November 2022

Background

The etiology of intellectual disabilities is diverse and includes both genetic and environmental factors. The genetic causes of intellectual disabilities range from chromosomal aberrations to single gene disorders. The TRAPPC9 gene has been reported to cause autosomal recessive forms of intellectual disabilities in 56 patients from consanguineous and non-consanguineous families around the world.

Methods

We analyzed two siblings with intellectual disability, microcephaly and delayed motor and speech development from a consanguineous Sudanese family. Genomic DNA was screened for mutations using NGS panel (NextSeq500 Illumina) testing 173 microcephaly associated genes in the Molecular Genetics service in Robert Debre hospital in Paris, France.

Results

A novel homozygous mutation (NM_031466.7 (TRAPPC9):c.2288dup, p. (Val764Glyfs*7) in exon 14 of TRAPPC9 gene was found in the two patients. The mutation was predicted to cause nonsense mediated decay (NSMD) using SIFT prediction tool. The variant has not been found in either gnomAD or Exac databases. Both parents were heterozygous (carriers) to the mutation.

Conclusion

This is the first study to report patients with TRAPPC9-related disorder from Sub-Saharan Africa.
Cancer-derived extracellular succinate: a driver of cancer metastasis
Authors: Kuo Cheng-Chin , Wu Jing-Yiing , Wu Kenneth K.
Published: November 2022

Succinate is a tricarboxylic acid (TCA) cycle intermediate normally confined to the mitochondrial matrix. It is a substrate of succinate dehydrogenase (SDH). Mutation of SDH subunits (SDHD and SDHB) in hereditary tumors such as paraganglioma or reduction of SDHB expression in cancer results in matrix succinate accumulation which is transported to cytoplasma and secreted into the extracellular milieu. Excessive cytosolic succinate is known to stabilize hypoxia inducible factor-1α (HIF-1α) by inhibiting prolyl hydroxylase. Recent reports indicate that cancer-secreted succinate enhances cancer cell migration and promotes cancer metastasis by activating succinate receptor-1 (SUCNR-1)-mediated signaling and transcription pathways. Cancer-derived extracellular succinate enhances cancer cell and macrophage migration through SUCNR-1 → PI-3 K → HIF-1α pathway. Extracellular succinate induces tumor angiogenesis through SUCNR-1-mediated ERK1/2 and STAT3 activation resulting in upregulation of vascular endothelial growth factor (VEGF) expression. Succinate increases SUCNR-1 expression in cancer cells which is considered as a target for developing new anti-metastasis drugs. Furthermore, serum succinate which is elevated in cancer patients may be a theranostic biomarker for selecting patients for SUCNR-1 antagonist therapy.
CHRNB2 represses pancreatic cancer migration and invasion via inhibiting β-catenin pathway
Authors: Qin Cheng , Li Tianhao , Wang Yuanyang , Zhao Bangbo , Li Zeru , Li Tianyu , Yang Xiaoying , Zhao Yutong , Wang Weibin
Published: November 2022

Background

Pancreatic cancer is one of the most lethal disease with highly fatal and aggressive properties. Lymph node ratio (LNR), the ratio of the number of metastatic lymph nodes to the total number of examined lymph nodes, is an important index to assess lymphatic metastasis and predict prognosis, but the molecular mechanism underlying high LNR was unclear.

Methods

Gene expression and clinical information data of pancreatic cancer were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Patients in TCGA were averagely divided into low and high LNR groups. Then, Weighted Gene Co-expression Network Analysis (WGCNA) was utilized to build co-expression network to explore LNR-related modules and hub genes. GO and KEGG analysis was performed to find key pathways related to lymph node metastasis. Next, GSE101448 and the overall survival data in TCGA was employed to further select significant genes from hub genes. Considering the key role of CHRNB2 in LNR and survival, gene set enrichment analysis (GSEA) was applied to find pathways related to CHRNB2 expression in pancreatic cancer. The contribution of CHRNB2 to migrative and invasive ability of pancreatic cancer cells was confirmed by Transwell assays. We finally explored the role of CHRNB2 in EMT and β-catenin pathway via Western Blot.

Results

High LNR was significantly related to high T stages and poor prognosis. In WGCNA, 14 hub genes (COL5A1, FN1, THBS2, etc.) were positively related to high LNR, 104 hub genes (FFAR1, SCG5, TMEM63C, etc.) were negatively related to high LNR. After taking the intersection with GSE101448, 13 genes (CDK5R2, SYT7, CACNA2D2, etc.) which might prevent lymph node metastasis were further selected. Among them, CHRNB2 showed the strongest relationship with long survival. Moreover, CHRNB2 also negatively related to the T stages and LNR. Next, knockdown of CHRNB2 expression could acetylcholine (ACh)-independently increase the migration and invasion of pancreatic cancer cells, while CHRNB2 overexpression ACh-independently decrease the migration and invasion of pancreatic cancer cells. For exploring the underlying mechanism, CHRNB2 downregulated β-catenin pathway might through controlling its upstream regulators such as SOX6, SRY, SOX17, and TCF7L2.

Conclusions

CHRNB2 negatively relates to lymph node metastasis in pancreatic cancer patients. CHRNB2 could inhibit β-catenin pathway, EMT, migration and invasion of pancreatic cancer cells via ACh-independent mechanism.
Achieving malaria testing and treatment targets for children under five in Mozambique: a cost-effectiveness analysis
Authors: Avanceña Anton L. V. , Miller Angie , Canana Neide , Dula Janeth , Saifodine Abuchahama , Cadrinho Baltazar , Maffioli Elisa M.
Published: November 2022

Background

The entire population of Mozambique is at risk for malaria, which remains one of the leading causes of death. The 2017–2022 National Malaria Strategic Plan focuses on reducing malaria morbidity and mortality in high- and low-transmission areas. This study aimed to estimate the costs and health benefits of six variations of the World Health Organization’s “test-and-treat” strategy among children under five.

Methods

A decision tree model was developed that estimates the costs and health outcomes for children under five. Data on probabilities, costs, weights for disability-adjusted life years (DALYs), and quality-adjusted life years (QALYs) were based on peer-reviewed, grey literature, and primary data analysis of the 2018 Malaria Indicator Survey. Six scenarios were compared to the status quo and calculated the incremental cost-effectiveness ratio (ICER) in terms of cost per QALY gained, DALY averted, and life saved. Deterministic and probabilistic sensitivity analyses were conducted to understand the effect of parameter uncertainty on the findings.

Results

In the base case, reaching the target of 100% testing with rapid diagnostic tests (RDTs; Scenario 1) is more cost-effective than improving the testing rate alone by 10% (Scenario 2). Achieving a 100% (Scenario 3) or a 10% increase in treatment rate (Scenario 4) have ICERs that are lower than Scenarios 1 and 2. Both Scenarios 5 and 6, which represent combinations of Scenarios 1–4, have lower ICERs than their constituent strategies on their own, which suggests that improvements in treatment are more cost-effective than improvements in testing alone. These results held when DALYs averted or lives saved were used as health outcomes. Deterministic and probabilistic sensitivity analyses revealed that the cost-effectiveness of Scenarios 1–6 are subject sensitive to parameter uncertainty, though Scenarios 4 and 5 are the optimal choice when DALYs averted or QALYs gained were used as the measure of health outcomes across all cost-effectiveness thresholds.

Conclusions

Improving testing rates alone among children at risk for malaria has the potential to improve health but may not be the most efficient use of limited resources. Instead, small or large improvements in treatment, whether alone or in conjunction with improvements in testing, are the most cost-effective strategies for children under five in Mozambique.
Accelerated amyloid angiopathy and related vascular alterations in a mixed murine model of Alzheimer´s disease and type two diabetes
Authors: Vargas-Soria Maria , Ramos-Rodriguez Juan Jose , del Marco Angel , Hierro-Bujalance Carmen , Carranza-Naval Maria Jose , Calvo-Rodriguez Maria , van Veluw Susanne J. , Stitt Alan W. , Simó Rafael , Bacskai Brian J. , Infante-Garcia Carmen , Garcia-Alloza Monica
Published: November 2022

Background

While aging is the main risk factor for Alzheimer´s disease (AD), emerging evidence suggests that metabolic alterations such as type 2 diabetes (T2D) are also major contributors. Indeed, several studies have described a close relationship between AD and T2D with clinical evidence showing that both diseases coexist. A hallmark pathological event in AD is amyloid-β (Aβ) deposition in the brain as either amyloid plaques or around leptomeningeal and cortical arterioles, thus constituting cerebral amyloid angiopathy (CAA). CAA is observed in 85–95% of autopsy cases with AD and it contributes to AD pathology by limiting perivascular drainage of Aβ.

Methods

To further explore these alterations when AD and T2D coexist, we have used in vivo multiphoton microscopy to analyze over time the Aβ deposition in the form of plaques and CAA in a relevant model of AD (APPswe/PS1dE9) combined with T2D (db/db). We have simultaneously assessed the effects of high-fat diet-induced prediabetes in AD mice. Since both plaques and CAA are implicated in oxidative-stress mediated vascular damage in the brain, as well as in the activation of matrix metalloproteinases (MMP), we have also analyzed oxidative stress by Amplex Red oxidation, MMP activity by DQ™ Gelatin, and vascular functionality.

Results

We found that prediabetes accelerates amyloid plaque and CAA deposition, suggesting that initial metabolic alterations may directly affect AD pathology. T2D significantly affects vascular pathology and CAA deposition, which is increased in AD-T2D mice, suggesting that T2D favors vascular accumulation of Aβ. Moreover, T2D synergistically contributes to increase CAA mediated oxidative stress and MMP activation, affecting red blood cell velocity.

Conclusions

Our data support the cross-talk between metabolic disease and Aβ deposition that affects vascular integrity, ultimately contributing to AD pathology and related functional changes in the brain microvasculature.
Deep learning in CT image segmentation of cervical cancer: a systematic review and meta-analysis
Authors: Yang Chongze , Qin Lan-hui , Xie Yu-en , Liao Jin-yuan
Published: November 2022

Background

This paper attempts to conduct a systematic review and meta-analysis of deep learning (DLs) models for cervical cancer CT image segmentation.

Methods

Relevant studies were systematically searched in PubMed, Embase, The Cochrane Library, and Web of science. The literature on DLs for cervical cancer CT image segmentation were included, a meta-analysis was performed on the dice similarity coefficient (DSC) of the segmentation results of the included DLs models. We also did subgroup analyses according to the size of the sample, type of segmentation (i.e., two dimensions and three dimensions), and three organs at risk (i.e., bladder, rectum, and femur). This study was registered in PROSPERO prior to initiation (CRD42022307071).

Results

A total of 1893 articles were retrieved and 14 articles were included in the meta-analysis. The pooled effect of DSC score of clinical target volume (CTV), bladder, rectum, femoral head were 0.86(95%CI 0.84 to 0.87), 0.91(95%CI 0.89 to 0.93), 0.83(95%CI 0.79 to 0.88), and 0.92(95%CI 0.91to 0.94), respectively. For the performance of segmented CTV by two dimensions (2D) and three dimensions (3D) model, the DSC score value for 2D model was 0.87 (95%CI 0.85 to 0.90), while the DSC score for 3D model was 0.85 (95%CI 0.82 to 0.87). As for the effect of the capacity of sample on segmentation performance, no matter whether the sample size is divided into two groups: greater than 100 and less than 100, or greater than 150 and less than 150, the results show no difference (P > 0.05). Four papers reported the time for segmentation from 15 s to 2 min.

Conclusion

DLs have good accuracy in automatic segmentation of CT images of cervical cancer with a less time consuming and have good prospects for future radiotherapy applications, but still need public high-quality databases and large-scale research verification.
Mutation spectrum of chinese amyotrophic lateral sclerosis patients with frontotemporal dementia
Authors: Yang Xunzhe , Sun Xiaohai , Liu Qing , Liu Liyang , Li Jinyue , Cai Zhengyi , Zhang Kang , Liu Shuangwu , He Di , Shen Dongchao , Liu Mingsheng , Cui Liying , Zhang Xue
Published: November 2022

Background

Studies have reported that a noncoding hexanucleotide repeat in C9ORF72, is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) among Caucasian population, nevertheless it is rare in Chinese population. Therefore, we aimed to investigate the mutation spectrum of Chinese ALS patients with FTD (ALS-FTD).

Methods

ALS patients with and without cognitive impairments were enrolled. Clinical features were collected including age, sex, disease duration, ALSFRS-r, family history and cognitive evaluation. Thirty-six ALS genes were screened by whole exome sequencing (WES) and repeat-primed polymerase chain reaction (PCR) were used for detection of and abnormal repeat expansions of C9ORF72.

Results

A total of 1208 patients, including 66 familial ALS (FALS) and 1142 sporadic ALS (SALS) patients were included. Twenty-three patients with sporadic ALS and one familial ALS index had concomitant FTD, which accounts for 1.99% (24/1208) of patients with ALS. In sporadic ALS-FTD, one case harboring C9ORF72 expansion variant, two cases harboring ANXA11 variants and one individual carrying CCNF variant were identified. A recurrent UBQLN2 variant was detected in a familial ALS-FTD patient. All of the ALS-FTD patients carrying variants in known causative genes manifested motor symptom onset (two bulbar onset and three limb onset) and developed cognitive impairment thereafter. It is not easy to draw a conclusion of the genotype-phenotype association in ALS-FTD with certain variants, limited by the small number of patients.

Conclusion

Our findings provide an overview of spectrum of genetic variants in Chinese ALS-FTD patients. Variants of uncertain significance in UBQLN2, ANXA11 and CCNF were identified and further studies are required for causal relations of these variants with ALS-FTD.
Global child and adolescent mental health perspectives: bringing change locally, while thinking globally
Authors: Kaku Sowmyashree Mayur , Sibeoni Jordan , Basheer Salah , Chang Jane Pei-Chen , Dahanayake Dulangi Maneksha Amerasinghe , Irarrazaval Matias , Lachman Jamie M , Mapayi Boladale Moyosore , Mejia Anilena , Orri Massimiliano , Jui-Goh Tze , Uddin Md Saleh , Vallance Inge
Published: November 2022

Child and adolescent mental health (CAMH) are a global priority. Different countries across the globe face unique challenges in CAMH services that are specific to them. However, there are multiple issues that are also similar across countries. These issues have been presented in this commentary from the lens of early career CAMH professionals who are alumni of the Donald J Cohen Fellowship program of the IACAPAP. We also present recommendations that can be implemented locally, namely, how promoting mental health and development of children and adolescents can result in better awareness and interventions, the need to improve quality of care and access to care, use of technology to advance research and practices in CAMH, and how investing in research can secure and support CAMH professionals and benefit children and adolescents across the globe. As we continue to navigate significant uncertainty due to dynamic circumstances globally, bolstering collaborations by “bringing change locally, while thinking globally” are invaluable to advancing global CAMH research, clinical service provision, and advancement of the field.
A genome-wide association study of mammographic texture variation
Authors: Liu Yuxi , Chen Hongjie , Heine John , Lindstrom Sara , Turman Constance , Warner Erica T. , Winham Stacey J. , Vachon Celine M. , Tamimi Rulla M. , Kraft Peter , Jiang Xia
Published: November 2022

Background

Breast parenchymal texture features, including grayscale variation (V), capture the patterns of texture variation on a mammogram and are associated with breast cancer risk, independent of mammographic density (MD). However, our knowledge on the genetic basis of these texture features is limited.

Methods

We conducted a genome-wide association study of V in 7040 European-ancestry women. V assessments were generated from digitized film mammograms. We used linear regression to test the single-nucleotide polymorphism (SNP)-phenotype associations adjusting for age, body mass index (BMI), MD phenotypes, and the top four genetic principal components. We further calculated genetic correlations and performed SNP-set tests of V with MD, breast cancer risk, and other breast cancer risk factors.

Results

We identified three genome-wide significant loci associated with V: rs138141444 (6q24.1) in ECT2L, rs79670367 (8q24.22) in LINC01591, and rs113174754 (12q22) near PGAM1P5. 6q24.1 and 8q24.22 have not previously been associated with MD phenotypes or breast cancer risk, while 12q22 is a known locus for both MD and breast cancer risk. Among known MD and breast cancer risk SNPs, we identified four variants that were associated with V at the Bonferroni-corrected thresholds accounting for the number of SNPs tested: rs335189 (5q23.2) in PRDM6, rs13256025 (8p21.2) in EBF2, rs11836164 (12p12.1) near SSPN, and rs17817449 (16q12.2) in FTO. We observed significant genetic correlations between V and mammographic dense area (rg = 0.79, P = 5.91 × 10−5), percent density (rg = 0.73, P = 1.00 × 10−4), and adult BMI (rg =  − 0.36, P = 3.88 × 10−7). Additional significant relationships were observed for non-dense area (z =  − 4.14, P = 3.42 × 10−5), estrogen receptor-positive breast cancer (z = 3.41, P = 6.41 × 10−4), and childhood body fatness (z =  − 4.91, P = 9.05 × 10−7) from the SNP-set tests.

Conclusions

These findings provide new insights into the genetic basis of mammographic texture variation and their associations with MD, breast cancer risk, and other breast cancer risk factors.