bluuebunny/crossref_metadata_2025 huggingface dataset:
The impact of exercise modalities on blood glucose, blood pressure and body composition in patients with type 2 diabetes mellitus
Authors: Ambelu Tensay , Teferi Getu
Published: November 2023

Background

Physical activity has been recommended as an important non-pharmacological therapeutic strategy for the management of type 2 diabetes mellitus (T2DM). The aim of this study was to investigate the effects of 12 weeks of strength, aerobic, and a combination of aerobic and resistance training on blood glucose level, blood pressure, and body composition in patients with T2DM.

Methods

From Debremarkos referral hospital, 40 subjects with T2DM (mean age 42.45 years, 29 men, 11 women) were randomly assigned to one of three intervention groups or the control group. The following variables were measured: body mass index (BMI), fasting blood glucose (FBG), systolic blood pressure (SBP), diastolic blood pressure (DBP), and body fat percentage (BFP). Paired sample T-test and one-way ANCOVA were applied whilst controlling for diet, gender, and age.

Results

All intervention groups showed improvement in a mean difference of FBG − 13.03 (t =-5.55, df = 39, p < 0.001), SBP − 21.63 mmHg − 17.6 mmHg (t =-6.51, df = 39, p < 0.001), DBP − 11.86 mmHg (t = -5.47, df = 39, p < 0.001) and BFP − 9.14 (t = -7.49, df = 39, p < 0.001). There was a significant difference in mean BMI reduction when diet, gender, and age were controlled in a one-way ANCOVA (F (3, 33) = 11.79, p < 0.001), SBP (F (3, 33) = 13.383, p < 0.001), DBP (F (3, 33) = 7.830, p < 0.001), FBG (F (3, 33) = 6.337, p < 0.001), BFP (F (3, 33) = 24.29, p < 0.001) between the exercise intervention groups and control group. Additionally, the estimated marginal means indicate that the combined strength and aerobic exercise intervention group experienced the greatest improvements.

Conclusion

Body composition, blood pressure, and fasting blood glucose were significantly lower in the combined (aerobic plus strength) treatment than in the individual treatment, indicating that the combined exercise intervention was more successful in altering these parameters.
Congenital erythropoietic porphyria presenting with recurrent epistaxis: a case report
Authors: Khan Javeriah , Hashmi Muhammad Usman , Noor Nabeeha , Khan Ahmad Jamal , Shrateh Oadi N. , Tahir Muhammad Junaid
Published: November 2023

Background

Congenital erythropoietic porphyria (CEP), also known as pink tooth or Gunther disease, is a rare hereditary disorder caused by an enzyme mutation in the heme biosynthesis pathway, which leads to the accumulation of immature and non-physiological protoporphyrin rings in various tissues. CEP is characterized by sun-exposed bullous skin lesions, hemolytic anemia, red/brown urine, and teeth staining.

Case presentation

We present a unique case of a 10-year-old Asian boy with CEP who presented with recurrent epistaxis, an unusual presentation for this condition. Based on clinical presentation and laboratory findings, including elevated urine uroporphyrin and coproporphyrin I and III levels, microcytic anemia, a higher red cell distribution width (RDW), and a lower platelet count, a thorough assessment and detailed workup resulted in a diagnosis of CEP. The patient underwent a successful splenectomy and recovered without any complications.

Conclusion

This case report aims to raise awareness among healthcare professionals about the uncommon and atypical presentation of CEP and its management options.
Human mesenchymal stem cells derived from adipose tissue showed a more robust effect than those from the umbilical cord in promoting corneal graft survival by suppressing lymphangiogenesis
Authors: Kang Huanmin , Feng Jianing , Peng Yingqian , Liu Yingyi , Yang Yalei , Wu Ying , Huang Jian , Jie Ying , Chen Baihua , He Yan
Published: November 2023

Background

Mesenchymal stem cells (MSCs) have shown promising potential in allograft survival. However, few reports have focused on comparing the immunosuppressive capacity of MSCs from different sources and administered via different routes in inhibiting transplant rejection. Moreover, virtually nothing is known about the role of MSCs in the regulation of graft neovascularization and lymphangiogenesis. In this study, we compared the efficacy of human adipose MSCs (hAD-MSCs) and human umbilical cord MSCs (hUC-MSCs) in vitro and in corneal transplantation models to explore the underlying molecular mechanisms and provide a powerful strategy for future clinical applications.

Methods

hAD-MSCs and hUC-MSCs were generated, and their self-renewal and multi-differentiation abilities were evaluated. The inhibitory effect of human MSCs (hMSCs) was examined by T-cell proliferation assays with or without transwell in vitro. Two MSCs from different sources were separately adoptively transferred in mice corneal transplantation (5 × 105 or 1 × 106/mouse) via topical subconjunctival or intravenous (IV) routes. Allograft survival was evaluated every other day, and angiogenesis and lymphomagenesis were quantitatively analyzed by immunofluorescence staining. The RNA expression profiles of hMSCs were revealed by RNA sequencing (RNA-seq) and verified by quantitative real-time PCR (qRT‒PCR), western blotting or ELISA. The function of the differentially expressed gene FAS was verified by a T-cell apoptosis assay.

Results

hAD-MSCs induced stronger immunosuppression in vitro than hUC-MSCs. The inhibitory effect of hUC-MSCs but not hAD-MSCs was mediated by cell–cell contact-dependent mechanisms. Systemic administration of a lower dose of hAD-MSCs showed better performance in prolonging corneal allograft survival than hUC-MSCs, while subconjunctival administration of hMSCs was safer and further prolonged corneal allograft survival. Both types of hMSCs could inhibit corneal neovascularization, while hAD-MSCs showed greater superiority in suppressing graft lymphangiogenesis. RNA-seq analysis and confirmation experiments revealed the superior performance of hAD-MSCs in allografts based on the lower expression of vascular endothelial growth factor C (VEGF-C) and higher expression of FAS.

Conclusions

The remarkable inhibitory effects on angiogenesis/lymphangiogenesis and immunological transplantation effects support the development of hAD-MSCs as a cell therapy against corneal transplant rejection. Topical administration of hMSCs was a safer and more effective route for application than systemic administration.
Bright ferritin for long-term MR imaging of human embryonic stem cells
Authors: Zhuang Keyu , Romagnuolo Rocco , Sadikov Valdman Tamilla , Vollett Kyle D. W. , Szulc Daniel A. , Cheng Hai-Ying Mary , Laflamme Michael A. , Cheng Hai-Ling Margaret
Published: November 2023

Background

A non-invasive imaging technology that can monitor cell viability, retention, distribution, and interaction with host tissue after transplantation is needed for optimizing and translating stem cell-based therapies. Current cell imaging approaches are limited in sensitivity or specificity, or both, for in vivo cell tracking. The objective of this study was to apply a novel ferritin-based magnetic resonance imaging (MRI) platform to longitudinal tracking of human embryonic stem cells (hESCs) in vivo.

Methods

Human embryonic stem cells (hESCs) were genetically modified to stably overexpress ferritin using the CRISPR-Cas9 system. Cellular toxicity associated with ferritin overexpression and manganese (Mn) supplementation were assessed based on cell viability, proliferation, and metabolic activity. Ferritin-overexpressing hESCs were characterized based on stem cell pluripotency and cardiac-lineage differentiation capability. Cells were supplemented with Mn and imaged in vitro as cell pellets on a preclinical 3 T MR scanner. T1-weighted images and T1 relaxation times were analyzed to assess contrast. For in vivo study, three million cells were injected into the leg muscle of non-obese diabetic severe combined immunodeficiency (NOD SCID) mice. Mn was administrated subcutaneously. T1-weighted sequences and T1 mapping were used to image the animals for longitudinal in vivo cell tracking. Cell survival, proliferation, and teratoma formation were non-invasively monitored by MRI. Histological analysis was used to validate MRI results.

Results

Ferritin-overexpressing hESCs labeled with 0.1 mM MnCl2 provided significant T1-induced bright contrast on in vitro MRI, with no adverse effect on cell viability, proliferation, pluripotency, and differentiation into cardiomyocytes. Transplanted hESCs displayed significant bright contrast on MRI 24 h after Mn administration, with contrast persisting for 5 days. Bright contrast was recalled at 4–6 weeks with early teratoma outgrowth.

Conclusions

The bright-ferritin platform provides the first demonstration of longitudinal cell tracking with signal recall, opening a window on the massive cell death that hESCs undergo in the weeks following transplantation before the surviving cell fraction proliferates to form teratomas.
GREB1L overexpression is associated with good clinical outcomes in breast cancer
Authors: Dong Ke , Geng Chenchen , Zhan Xiaohong , Sun Zhi , Pu Qian , Li Peng , Song Haiyun , Zhao Guanghui , Gao Haidong
Published: November 2023

Background

Breast cancer is the most common malignant tumor among women worldwide. GREB1L is a protein-coding gene. Previous studies have shown that GREB1L plays a vital role in lung and gastric adenocarcinoma. Currently, there is no relevant report about its role in breast cancer.

Methods

The Cancer Genome Atlas database was used to compare the expression level of GREB1L between tumor and normal tissues. The TISIDB website was used for prognosis analysis. The LinkedOmics database was used to predict the potential biological mechanism of GREB1L in breast cancer. Immunohistochemistry was used to detect the GREB1L expression level in breast tissue. Western blotting was used to detect the GREB1L expression level in cell lines. Transwell assays, CCK-8 cell proliferation assays, and colony formation assays were used to detect the migration, invasion, proliferation, and colony formation abilities of cells. Subcutaneous xenograft models were used to detect the in vivo tumor formation abilities of cells.

Results

GREB1L is highly expressed in breast cancer tissues and breast cancer cells. KEGG enrichment analysis suggested that GREB1L participates in the regulation of the Hedgehog signaling pathway; changes in GREB1L expression affected the migration and invasion abilities of MCF7 and MDA-MB-231 cells. Although changes in GREB1L expression did not affect their proliferation and colony formation abilities in vitro and in vivo, they affected the expression of tumor metastasis-related genes in vivo. The overexpression of GREB1L in breast cancer predicted a favorable prognosis.

Conclusion

These results showed that GREB1L is involved in the development of breast cancer, and it may be a potential molecular marker for predicting the prognosis of breast cancer.
Identification of genetic loci jointly influencing COVID-19 and coronary heart diseases
Authors: Wang Siyue , Peng Hexiang , Chen Feng , Liu Chunfang , Zheng Qiwen , Wang Mengying , Wang Jiating , Yu Huan , Xue Enci , Chen Xi , Wang Xueheng , Fan Meng , Qin Xueying , Wu Yiqun , Li Jin , Ye Ying , Chen Dafang , Hu Yonghua , Wu Tao
Published: November 2023

Background

Comorbidities of coronavirus disease 2019 (COVID-19)/coronary heart disease (CHD) pose great threats to disease outcomes, yet little is known about their shared pathology. The study aimed to examine whether comorbidities of COVID-19/CHD involved shared genetic pathology, as well as to clarify the shared genetic variants predisposing risks common to COVID-19 severity and CHD risks.

Methods

By leveraging publicly available summary statistics, we assessed the genetically determined causality between COVID-19 and CHD with bidirectional Mendelian randomization. To further quantify the causality contributed by shared genetic variants, we interrogated their genetic correlation with the linkage disequilibrium score regression method. Bayesian colocalization analysis coupled with conditional/conjunctional false discovery rate analysis was applied to decipher the shared causal single nucleotide polymorphisms (SNPs).

Findings

Briefly, we observed that the incident CHD risks post COVID-19 infection were partially determined by shared genetic variants. The shared genetic variants contributed to the causality at a proportion of 0.18 (95% CI 0.18–0.19) to 0.23 (95% CI 0.23–0.24). The SNP (rs10490770) located near LZTFL1 suggested direct causality (SNPs → COVID-19 → CHD), and SNPs in ABO (rs579459, rs495828), ILRUN(rs2744961), and CACFD1(rs4962153, rs3094379) may simultaneously influence COVID-19 severity and CHD risks.

Interpretation

Five SNPs located near LZTFL1 (rs10490770), ABO (rs579459, rs495828), ILRUN (rs2744961), and CACFD1 (rs4962153, rs3094379) may simultaneously influence their risks. The current study suggested that there may be shared mechanisms predisposing to both COVID-19 severity and CHD risks. Genetic predisposition to COVID-19 is a causal risk factor for CHD, supporting that reducing the COVID-19 infection risk or alleviating COVID-19 severity among those with specific genotypes might reduce their subsequent CHD adverse outcomes. Meanwhile, the shared genetic variants identified may be of clinical implications for identifying the target population who are more vulnerable to adverse CHD outcomes post COVID-19 and may also advance treatments of ‘Long COVID-19.’
Neurocognitive and mental health outcomes in children with tungiasis: a cross-sectional study in rural Kenya and Uganda
Authors: Otieno Berrick , Elson Lynne , Matharu Abneel K. , Riithi Naomi , Chongwo Esther , Katana Khamis , Nasambu Carophine , Mutebi Francis , Feldmeier Herman , Krücken Jürgen , Fillinger Ulrike , Abubakar Amina
Published: November 2023

Background

Tungiasis, a neglected tropical parasitosis, disproportionately affects children. Few empirical studies have reported neurocognitive and mental health outcomes of children with ectoparasitic skin diseases like tungiasis. Pathophysiology of tungiasis suggests it could detrimentally affect cognition and behaviour. This study pioneered the investigation of neurocognitive and mental health outcomes in children with tungiasis.

Methods

This was a multi-site cross-sectional study including 454 quasi-randomly sampled school-children aged 8–14 from 48 randomly selected schools in two counties in Kenya and a district in Uganda. The participants were stratified into infected and uninfected based on the presence of tungiasis. The infected were further classified into mild and severe infection groups based on the intensity of the infection. Adapted, validated, and standardized measures of cognition and mental health such as Raven Matrices and Child Behaviour Checklist were used to collect data. Statistical tests including a multilevel, generalized mixed-effects linear models with family link set to identity were used to compare the scores of uninfected and infected children and to identify other potential risk factors for neurocognitive and behavioural outcomes.

Results

When adjusted for covariates, mild infection was associated with lower scores in literacy [adjusted β(aβ) = − 8.9; 95% confidence interval (CI) − 17.2, − 0.6], language (aβ = − 1.7; 95% CI − 3.2, − 0.3), cognitive flexibility (aβ = − 6.1; 95% CI − 10.4, − 1.7) and working memory (aβ = − 0.3; 95% CI − 0.6, − 0.1). Severe infection was associated with lower scores in literacy (aβ = − 11.0; 95% CI − 19.3, − 2.8), response inhibition, (aβ = − 2.2; 95% CI − 4.2, − 0.2), fine motor control (aβ = − 0.7; 95% CI − 1.1, − 0.4) and numeracy (aβ = − 3; 95% CI − 5.5, − 0.4).

Conclusions

This study provides first evidence that tungiasis is associated with poor neurocognitive functioning in children. Since tungiasis is a chronic disease with frequent reinfections, such negative effects may potentially impair their development and life achievements.

Graphical abstract
Relevance and consequence of chronic inflammation for obesity development
Authors: Ruck Lisa , Wiegand Susanna , Kühnen Peter
Published: November 2023

Background

Increasing prevalence of morbid obesity accompanied by comorbidities like type 2 diabetes mellitus (T2DM) led to a demand for improving therapeutic strategies and pharmacological intervention options. Apart from genetics, inflammation processes have been hypothesized to be of importance for the development of obesity and related aspects like insulin resistance.

Main text

Within this review, we provide an overview of the intricate interplay between chronic inflammation of the adipose tissue and the hypothalamus and the development of obesity. Further understanding of this relationship might improve the understanding of the underlying mechanism and may be of relevance for the establishment of new treatment strategies.
Tau seed amplification assay reveals relationship between seeding and pathological forms of tau in Alzheimer’s disease brain
Authors: Frey Bryan , Holzinger David , Taylor Keenan , Ehrnhoefer Dagmar E. , Striebinger Andreas , Biesinger Sandra , Gasparini Laura , O’Neill Michael J. , Wegner Florian , Barghorn Stefan , Höglinger Günter U. , Heym Roland G.
Published: November 2023

Tau seed amplification assays (SAAs) directly measure the seeding activity of tau and would therefore be ideal biomarkers for clinical trials targeting seeding-competent tau in Alzheimer’s disease (AD). However, the precise relationship between tau seeding measured by SAA and the levels of pathological forms of tau in the AD brain remains unknown. We developed a new tau SAA based on full-length 0N3R tau with sensitivity in the low fg/ml range and used it to characterize 103 brain samples from three independent cohorts. Tau seeding clearly discriminated between AD and control brain samples. Interestingly, seeding was absent in Progressive Supranuclear Palsy (PSP) putamen, suggesting that our tau SAA did not amplify 4R tau aggregates from PSP brain. The specificity of our tau SAA for AD brain was further supported by analysis of matched hippocampus and cerebellum samples. While seeding was detected in hippocampus from Braak stages I-II, no seeding was present in AD cerebellum that is devoid of tau inclusions. Analysis of 40 middle frontal gyrus samples encompassing all Braak stages showed that tau SAA seeding activity gradually increased with Braak stage. This relationship between seeding activity and the presence of tau inclusions in AD brain was further supported by robust correlations between tau SAA results and the levels of phosphorylated tau212/214, phosphorylated tau181, aggregated tau, and sarkosyl-insoluble tau. Strikingly, we detected tau seeding in the middle frontal gyrus already at Braak stage II-III, suggesting that tau SAA can detect tau pathology earlier than conventional immunohistochemical staining. In conclusion, our data suggest a quantitative relationship between tau seeding activity and pathological forms of tau in the human brain and provides an important basis for further development of tau SAA for accessible human samples.
Lopadostoma, Oligostoma, and some Rosellinia specimens from the herbarium of the Swiss Federal Institute of Technology (ZT): the value of early fieldwork and the importance of keeping fungal collections
Authors: Petrini Liliane E.
Published: November 2023

Background

Morphology, hosts, and collecting sites of fungi assessed from herbarium material of special interest deserve to be brought to the attention of mycologists.

Results

Specimens of Lopadostoma and Oligostoma deposited at ZT are briefly described and listed to expand the knowledge about their distribution. Three yet unmentioned Rosellinia collections are reported. One could be identified as R. mastoidiformis, a second as R. neblina; both are known only from the type collections. The third one seems to be a yet undescribed taxon and is formally described as R. schueppii.

Conclusions

These observations emphasize the importance of keeping fungal collections and highlight the importance of field work and contributions by early mycologists.
Determination of the yield, enzymatic and metabolic response of two Capsicum spp. cultivars to deficit irrigation and fertilization using the stable isotope 15N
Authors: Zamljen Tilen , Lojen Sonja , Zupanc Vesna , Slatnar Ana
Published: November 2023

Background

Climate change is increasingly impacting agriculture all over the world, with extended periods of drought, flooding, hail, winds and temperature extremes. To negate the effects of climate change, researchers are trying to find new agricultural production techniques, to save resources without losing yield quality and quantity. A study on Capsicum annuum L. 'Chili-AS Rot' and Capsicum chinense Jacq. 'Naga Morich' chilies, grown under field capacity, deficit irrigation (50% field capacity) and full and half dose of mineral fertilizer in peat soil substrate was conducted. Both cultivars were marked with the stable isotope 15N, to follow nitrogen translocation in chili plants under stress conditions.

Results

The yield and plant biomass, capsaicin synthase (CS), phenylalanine ammonia lyase (PAL), and peroxidase (POX), as well as total and individual capsaicinoids were studied. In 'Chili-AS Rot' the deficit irrigation with the full-fertilization (Diff) dose showed the highest yield and fruit number, compared to other treatments. In the 'Naga Morich' cultivar the deficit irrigation and half-fertilization (Dihf), showed the highest yield, fruit number and dry weight of chilies, compared to other treatments. In the cultivar 'Chili-AS Rot', deficit irrigation was found to reduce the utilization of N fertilizer when the plant (leaves, stems, and roots) and fruit were considered. The utilization of nitrogen fertilizer was 60 to 70% under deficit fertilization, regardless of the irrigation treatment. The half dose fertilized plants of 'Chili-AS Rot' had higher CS activity and PAL activity (from 50 to 80%) than fully fertilized plants, with deficit irrigation having about 10% higher enzymatic activity than field-capacity irrigated plants. In 'Naga Morich', irrigation treatment affected lower enzymatic activity than field-capacity irrigated plants.

Conclusions

The results indicate that deficit irrigation and fertilization can be used to maintain enzymatic activity and thus capsaicinoid content, which could reduce the economic cost of irrigation water and fertilizer. It was confirmed that the yield was better under deficit irrigation and fertilization for the more pungent 'Naga Morich'. The result of the study shows that when water and fertilizer use is reduced by up to 50%, chili yield losses are minimal or non-existent.

Graphical Abstract
An automatic pipeline for PET/MRI attenuation correction validation in the brain
Authors: Hamdi Mahdjoub , Ying Chunwei , An Hongyu , Laforest Richard
Published: November 2023

Purpose

Challenges in PET/MRI quantitative accuracy for neurological uses arise from PET attenuation correction accuracy. We proposed and evaluated an automatic pipeline to assess the quantitative accuracy of four MRI-derived PET AC methods using analytically simulated PET brain lesions and ROIs as ground truth for PET activity.

Methods

Our proposed pipeline, integrating a synthetic lesion insertion tool and the FreeSurfer neuroimaging framework, inserts simulated spherical and brain ROIs into PET projection space, reconstructing them via four PET MRAC techniques. Utilizing an 11-patient brain PET dataset, we compared the quantitative accuracy of four MRACs (DIXON, DIXONbone, UTE AC, and DL-DIXON) against the gold standard PET CTAC, evaluating MRAC to CTAC activity bias in spherical lesions and brain ROIs with and without background activity against original (lesion free) PET reconstructed images.

Results

The proposed pipeline yielded accurate results for spherical lesions and brain ROIs, adhering to the MRAC to CTAC pattern of original brain PET images. Among the MRAC methods, DIXON AC exhibited the highest bias, followed by UTE, DIXONBone, and DL-DIXON showing the least. DIXON, DIXONbone, UTE, and DL-DIXON showed MRAC to CTAC biases of − 5.41%, − 1.85%, − 2.74%, and 0.08% respectively for ROIs inserted in background activity; − 7.02%, − 2.46%, − 3.56%, and − 0.05% for lesion ROIs without background; and − 6.82%, − 2.08%, − 2.29%, and 0.22% for the original brain PET images’ 16 FreeSurfer brain ROIs.

Conclusion

The proposed pipeline delivers accurate results for synthetic spherical lesions and brain ROIs, with and without background activity consideration, enabling the evaluation of new attenuation correction approaches without utilizing measured PET emission data. Additionally, it offers a consistent method to generate realistic lesion ROIs, potentially applicable in assessing further PET correction techniques.
Radiation exposure assessment of nuclear medicine staff administering [177Lu]Lu-DOTA-TATE with active and passive dosimetry
Authors: Riveira-Martin Mercedes , Struelens Lara , Muñoz Iglesias José , Schoonjans Werner , Tabuenca Olga , Nogueiras José Manuel , Salvador Gómez Francisco Javier , López Medina Antonio
Published: November 2023

Background

The use of lutetium-177 (177Lu)-based radiopharmaceuticals in peptide receptor nuclear therapy is increasing, but so is the number of nuclear medicine workers exposed to higher levels of radiation. In recent years, [177Lu]Lu-DOTA-TATE has begun to be widely used for the treatment of neuroendocrine tumours. However, there are few studies evaluating the occupational radiation exposure during its administration, and there are still some challenges that can result in higher doses to the staff, such as a lack of trained personnel or fully standardised procedures. In response, this study aims to provide a comprehensive analysis of occupational doses to the staff involved in the administration of [177Lu]Lu-DOTA-TATE.

Results

A total of 32 administrations of [177Lu]Lu-DOTA-TATE (7.4 GBq/session) carried out by a physician and a nurse, were studied. In total, two physicians and four nurses were independently monitored with cumulative (passive) and/or real-time (active) dosemeters. Extremity, eye lens and whole-body doses were evaluated in terms of the dosimetric quantities Hp(0.07), Hp(3) and Hp(10), respectively. It was obtained that lead aprons reduced dose rates and whole-body doses by 71% and 69% for the physicians, respectively, and by 56% and 68% for the nurses. On average, normalised Hp(10) values of 0.65 ± 0.18 µSv/GBq were obtained with active dosimetry, which is generally consistent with passive dosemeters. For physicians, the median of the maximum normalised Hp(0.07) values was 41.5 µSv/GBq on the non-dominant hand and 45.2 µSv/GBq on the dominant hand. For nurses 15.4 µSv/GBq on the non-dominant and 13.9 µSv/GBq on the dominant hand. The ratio or correction factor between the maximum dose measured on the hand and the dose measured on the base of the middle/ring finger of the non-dominant hand resulted in a factor of 5/6 for the physicians and 3/4 for the nurses. Finally, maximum normalised Hp(3) doses resulted in 2.02 µSv/GBq for physicians and 1.76 µSv/GBq for nurses.

Conclusions

If appropriate safety measures are taken, the administration of [177Lu]Lu-DOTA-TATE is a safe procedure for workers. However, regular monitoring is recommended to ensure that the annual dose limits are not exceeded.
Resection of anorectal fistula cancer associated with Crohn’s disease after preoperative chemoradiotherapy: a case report
Authors: Inoue Takuya , Sekido Yuki , Ogino Takayuki , Hata Tsuyoshi , Miyoshi Norikatsu , Takahashi Hidekazu , Uemura Mamoru , Mizushima Tsunekazu , Doki Yuichiro , Eguchi Hidetoshi
Published: November 2023

Background

Anorectal fistula cancer is often diagnosed in an advanced state, and radical resection is difficult when invasion of the pelvic wall is observed. In addition, there is currently no clear evidence for perioperative treatment of locally advanced cases. We report a case of anorectal fistula cancer with widespread infiltration diagnosed during the course of Crohn’s disease, which was curatively resected after preoperative chemoradiotherapy.

Case presentation

A 49-year-old man who had been diagnosed with Crohn’s disease (ileocolonic type) at the age of 25 and was found to have an anorectal fistula and perianal abscess at the age of 44 was referred to our department with complaints of abdominal pain and diarrhea. Computed tomography (CT) showed anal stenosis due to a pelvic mass. Pathological analysis of a biopsy taken under general anesthesia indicated mucinous carcinoma. Magnetic resonance imaging (MRI) revealed infiltration into the prostate, seminal vesicles, levator ani muscle, and left internal obturator muscle, and the patient was diagnosed with cT4N0M0 cStage IIIB anorectal fistula cancer (UICC TNM classification 8th edition). After performing a laparoscopic sigmoid colostomy, chemoradiation therapy (capecitabine + oxaliplatin, 50.4 Gy/28fr) was initiated. The patient then underwent laparoscopic total pelvic exenteration, colonic conduit diversion, extensive perineal resection, and reconstruction using bilateral gluteus maximus flaps and a right rectus abdominis musculocutaneous flap. The pathological diagnosis was mucinous adenocarcinoma, pT4, and all margins were negative. No recurrence was evident 6 months after the operation without adjuvant chemotherapy.

Conclusion

We described a case of curative resection after preoperative chemoradiotherapy for anorectal fistula cancer with extensive invasion that was diagnosed during the course of Crohn’s disease.An accumulation of cases is needed to determine the usefulness of preoperative chemoradiation therapy for local control of anorectal fistula cancer associated with Crohn’s disease.
Axillary cutaneous metastasis of colon cancer with microsatellite instability-high and BRAF V600E mutation treated with curative-intent surgery: a case report
Authors: Yamai Daisuke , Shimada Yoshifumi , Ozeki Hikaru , Matsumoto Akio , Abe Kaoru , Tajima Yosuke , Nakano Mae , Ichikawa Hiroshi , Sakata Jun , Wakai Toshifumi
Published: November 2023

Background

Colorectal cancer (CRC) metastasizes to various organs, while cutaneous metastases are rare. Although there have been several previous reports of axillary cutaneous metastases with other metastases of CRC, there has never been a report of axillary cutaneous metastasis of CRC that could be treated with curative-intent surgery.

Case presentation

A 68-year-old female was diagnosed with an axillary cutaneous tumor and ascending colon cancer with invasion to the duodenum. Histopathological and immunohistochemical analysis revealed that the axillary cutaneous tumor showed adenocarcinoma and the same expression pattern for cytokeratin 7, cytokeratin 20, and CDX2 as the ascending colon cancer, and that proved to be KRAS–NRAS wild type, MSI-H, and with a BRAF V600E mutation. The patient underwent a two-stage resection with curative intent after receiving neoadjuvant chemotherapy which consisted of one cycle of modified FOLFOX6 followed by two cycles of FOLFOXIRI. During and after the two operations, the patient received a total of nine cycles of modified FOLFOX6 as adjuvant chemotherapy. Two years after the initial surgery, and 1 year and 8 months after the second surgery, the patient is alive without recurrence.

Conclusions

To the best of our knowledge, this is the first report of axillary cutaneous metastasis of CRC with microsatellite instability-high and BRAF V600E mutation that could be treated with curative-intent surgery. It is important to recognize the presence of such cases for the accurate diagnosis and treatment of CRC with cutaneous metastasis.
Prevalence and risk factors of vitamin D deficiency among patients with chronic myofascial pain syndrome: a cross-sectional study
Authors: Channarong Pimpitcha , Phongamwong Chanwit
Published: November 2023

Background

Myofascial pain syndrome (MPS) is a common muscle condition characterized by painful trigger points. Vitamin D deficiency has been recognized as a precipitating factor of MPS. The present study aimed to determine the prevalence and risk factors of vitamin D deficiency in patients with chronic MPS.

Methods

A cross-sectional study was conducted, using a structured face-to-face interview to collect demographic information, clinical characteristics, pain duration and location, as well as the bodily pain subscale of SF36 and EQ-5D-5 L. The Elecsys vitamin D total II assay was used to measure serum total 25-hydroxyvitamin D level.

Results

Of 120 participants, vitamin D insufficiency (20 to 29.9 ng/ml) and deficiency (< 20 ng/ml) were 47.5% (95% CI: 38.3–56.8%) and 34.2% (95% CI: 25.8–43.4%), respectively. The adjusted odds ratios for vitamin D deficiency of participants aged < 45 years and who reported having ≤ 15 min sunlight exposure per day were 3.5 (95% CI: 1.54 to 7.98) and 2.38 (95% CI: 1.05 to 5.26), respectively. The bodily pain score (r = − 0.02, P = 0.86) and EQ-5D-5 L utility (r = 0.04, P = 0.66) did not significantly correlate with vitamin D levels.

Conclusion

Approximately one third of patients with chronic MPS had vitamin D deficiency. Age < 45 years and sunlight exposure ≤ 15 min/day were identified as potential risk factors for vitamin D deficiency in MPS patients.
Pericapsular nerve group block for osteoarthritis-related chronic hip joint pain: a case report
Authors: Sato Reiko , Kato Rina , So MinHye , Sugiura Takeshi , Sobue Kazuya
Published: November 2023

Background

Pericapsular nerve group (PENG) block has shown effectiveness for acute hip pain associated with fractures and surgery. Herein, PENG block was performed for osteoarthritis (OA)-related chronic hip joint pain.

Case presentation

A 65-year-old woman presented left hip pain. She had bilateral hip osteoarthritis that improved with medications; however, a fall resulted in left hip pain. She experienced severe pain on movements, which required walking aids. To alleviate the hip pain, a PENG block was performed under ultrasound guidance. Transient muscle weakness occurred in 2 of 5 times. After 5 blocks, she regained the ability to walk without assistive devices. Pain did not recur even after 6 months.

Conclusions

Repeated PENG blocks of short-acting local anesthetics alone could be an effective pain management technique for chronic hip pain. For safety, the appropriate injection site and local anesthetic dosage must be carefully considered.
The new wave of Congo virus in Pakistan: emerging threat
Authors: Masood Isra , Tahir Muhammad Junaid , Naeem Ather , Shrateh Oadi N. , Ahmed Ali
Published: November 2023

Congo virus, or Crimean–Congo hemorrhagic fever (CCHF), is a tick-borne disease caused by a single-stranded RNA virus (genus nairovirus, Bunyaviridae family). It spreads through infected ticks' bites or contact with viremic individuals or livestock. Factors supporting its spread include hot, humid climates, limited pesticide use, poor animal control, inadequate irrigation during monsoons, and vector control deficiencies. Nosocomial transmission in under-resourced hospitals poses a threat to healthcare workers. Decades of CCHF cases persist in Pakistan due to these factors, with six deaths reported by June 2023. To combat the epidemic, Pakistan should raise awareness, improve irrigation, establish surveillance systems, and implement livestock quarantine and vaccination.
Analysis of grounding system transient with consideration of soil ionization and mutual coupling effect
Authors: Sengar Kaushal Pratap , Chandrasekaran Kandasamy
Published: November 2023

The grounding system of an electrical substation provides safety to both operator and equipment. The lightning current waveform has a major influence on the dynamic performance of ground electrodes. If lightning current is large enough, soil will be ionized, which will have a great effect on the transient performance of the grounding system. Many numerical models have been developed to evaluate the transient performance of grounding system, still it is a challenging task to analyze the impulse behavior of grounding system efficiently. In this paper, the transient behavior of grounding systems with consideration of nonlinear and dynamic effects of soil ionization is presented. Grounding systems such as vertical rod, horizontal conductor and grounding grid buried in the homogeneous soil are considered as case study. Proposed model is the combination of circuit theory approach and method of moment with consideration of frequency-dependent impedance and mutual coupling effect between the conductor segments. Self and mutual component of inductance and resistance are considered in the analysis. Initially, transient performance of grounding system is analyzed for single vertical rod, horizontal and square grounding electrodes, further it is extended for vertical rod (more than one), horizontal conductor and grounding grids with different configurations. The analysis of grounding system with the consideration of mutual coupling effect is compared with devoid of mutual coupling, and differences between them are evaluated. For validating the developed method, simulated results are compared with the results reported in the literature, and good agreements are found. Analysis shows that the grounding impulse impedance decreased with increasing the magnitude of injected current. Developed method will help to improve the modeling of simple as well as complex grounding system buried in homogeneous soil.
Epigastric heteropagus twinning with dextrocardia: a case report
Authors: Siddiqua Ayesha , Noor-ul-Sabah  , Bhutta Muhammad Ramzan
Published: November 2023

Background

Heteropagus twinning is a rare birth defect in 1 in million live births. Epigastric heteropagus is the most frequent type, in which a smaller dependent (parasite twin) is attached to the body of the host (autosite twin) to the thorax and umbilicus. Several congenital anomalies have been previously described in the host twin. We describe the first case of epigastric heteropagus twinning with dextrocardia and situs inversus in which a successful surgical separation is performed.

Case presentation

A 48-h-old female sex twins were presented to Bahawal Victoria Hospital. A careful anatomic study using contrast X-ray, magnetic resonance imaging, and echocardiogram showed epigastric heteropagus twinning and situs inversus in autosite twin. A successful surgical separation was performed, and the parasite twin was removed from the body of the autosite twin.

Conclusions

Antepartum screening detects congenital malformations; however, several pregnancies are unsupervised in underdeveloped countries. In the case of heteropagus twinning, careful surgical separation in the absence of complications leads to the favorable survival of the autosite twin.
Effect of prematurely primary front teeth loss with anterior esthetic fixed appliance on fricative production in Arabic-speaking children
Authors: Sidhom Rania Makram , Melegy Reham Abd El-Waheed , Hosary Amina Mohamed El Nabawy El , Deen Shaima Mohamed Serag El
Published: November 2023

Background

Primary teeth affect the life quality regarding chewing, speech production, esthetics, and psychological well-being. Young children usually lose their primary maxillary incisors due to trauma or care and that leads to fault production of alveolar and dental fricatives. Fixed esthetic appliance replacing the lost primary front teeth were inserted and fricative sounds /s/,/s/,/∫ /,/z/and /z/ were tested before and after insertion of the fixed appliance through different time intervals.

Results

Improvement of fricative sound production occurred after fixed appliance insertion the /s/ sound, followed by /s/ sound showed immediate improvement while the /∫ / sound was the least to be improved even after 1 month duration. Both sounds /z/ and /z/ sound showed distortion immediately.

Conclusion

Premature loss of primary incisors in young children has a significant impact on speech production.
Endonasal endoscopic nasopharyngectomy for nasopharyngeal malignancies: a survival analysis
Authors: Iftikhar Haissan , Awan Muhammad Ozair , Ahmed Shahzada Khuram
Published: November 2023

Introduction

Nasopharyngeal cancer has a global incidence of less than 1.0 per 100,000 person-years. It originates from nasopharyngeal mucosa with the Fossa of Rosenmuller being the most common site. Radiation therapy with or without chemotherapy is an established first-line treatment modality given the sensitivity of the tumor.

Objectives

The aim of our study was to report survival outcomes amongst patients undergoing endonasal endoscopic nasopharyngectomy at a tertiary care referral center.

Methods

We conducted a retrospective longitudinal cohort study. We collected data on age, gender, prior treatment, histology, extent of surgery, post-operative adjuvant therapy, and recurrence and reported the survival along mean survival time using Kaplan–Meier curves and log-rank test.

Results

A total of six patients, three males and three females with a mean age of 43.7 years were included in our study. Of the six, three patients underwent a salvage procedure whereas three patients received upfront definitive surgical resection. Three patients developed recurrence with a mean survival time of 19.3 months. The disease-free survival at 1 and 2 years of surgery was 88.3% and 66% respectively.

Conclusion

Endonasal endoscopic nasopharyngectomy is an effective surgical procedure that can be undertaken for both salvage and primary cases. Our survival results are comparable to the literature.
Prediction of Adjuvant Gemcitabine Sensitivity in Resectable Pancreatic Adenocarcinoma Using the GemPred RNA Signature: An Ancillary Study of the PRODIGE-24/CCTG PA6 Clinical Trial
Authors: Nicolle Rémy , Bachet Jean-Baptiste , Harlé Alexandre , Iovanna Juan , Hammel Pascal , Rebours Vinciane , Turpin Anthony , Ben Abdelghani Meher , Wei Alice , Mitry Emmanuel , Lopez Anthony , Biagi James , François Eric , Artru Pascal , Lambert Aurélien , Renouf Daniel J. , Monard Laure , Mauduit Marjorie , Dusetti Nelson , Conroy Thierry , Cros Jérome
Published: November 2023

PURPOSE

GemPred, a transcriptomic signature predictive of the efficacy of adjuvant gemcitabine (GEM), was developed from cell lines and organoids and validated retrospectively. The phase III PRODIGE-24/CCTG PA6 trial has demonstrated the superiority of modified folinic acid, fluorouracil, irinotecan, and oxaliplatin (mFOLFIRINOX) over GEM as adjuvant therapy in patients with resected pancreatic ductal adenocarcinoma at the expense of higher toxicity. We evaluated the potential predictive value of GemPred in this population.

PATIENTS AND METHODS

Routine formalin-fixed paraffin-embedded surgical specimens of 350 patients were retrieved for RNA sequencing and GemPred prediction (167 in the GEM arm and 183 in the mFOLFIRINOX [mFFX] arm). Survival analyses were stratified by resection margins, lymph node status, and cancer antigen 19-9 level.

RESULTS

Eighty-nine patients' tumors (25.5%) were GemPred+ and were thus predicted to be gemcitabine-sensitive. In the GEM arm, GemPred+ patients (n = 50, 30%) had a significantly longer disease-free survival (DFS) than GemPred– patients (n = 117, 70%; median 27.3 v 10.2 months, hazard ratio [HR], 0.43 [95% CI, 0.29 to 0.65]; P < .001) and cancer-specific survival (CSS; median 68.4 v 28.6 months, HR, 0.42 [95% CI, 0.27 to 0.66]; P < .001). GemPred had no prognostic value in the mFFX arm. DFS and CSS were similar in GemPred+ patients who received adjuvant GEM and mFFX (median 27.3 v 24.0 months, and 68.4 v 51.4 months, respectively). The statistical interaction between GEM and GemPred+ status was significant for DFS ( P = .008) and CSS ( P = .004). GemPred+ patients had significantly more adverse events of grade ≥3 in the mFFX arm (76%) compared with those in the GEM arm (40%; P = .001).

CONCLUSION

This ancillary study of a phase III randomized trial demonstrates that among the quarter of patients with a GemPred-positive transcriptomic signature, survival was comparable with that of mFOLFIRINOX, whereas those receiving adjuvant gemcitabine had fewer adverse events.
Perioperative Atezolizumab Plus Fluorouracil, Leucovorin, Oxaliplatin, and Docetaxel for Resectable Esophagogastric Cancer: Interim Results From the Randomized, Multicenter, Phase II/III DANTE/IKF-s633 Trial
Authors: Lorenzen Sylvie , Götze Thorsten Oliver , Thuss-Patience Peter , Biebl Matthias , Homann Nils , Schenk Michael , Lindig Udo , Heuer Vera , Kretzschmar Albrecht , Goekkurt Eray , Haag Georg Martin , Riera-Knorrenschild Jorge , Bolling Claus , Hofheinz Ralf-Dieter , Zhan Tianzuo , Angermeier Stefan , Ettrich Thomas Jens , Siebenhuener Alexander Reinhard , Elshafei Moustafa , Bechstein Wolf Otto , Gaiser Timo , Loose Maria , Sookthai Disorn , Kopp Christina , Pauligk Claudia , Al-Batran Salah-Eddin ,   for the AIO and SAKK Study Working Groups
Published: November 2023

PURPOSE

This trial evaluates the addition of the PD-L1 antibody atezolizumab (ATZ) to standard-of-care fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) as a perioperative treatment for patients with resectable esophagogastric adenocarcinoma (EGA).

METHODS

DANTE started as multicenter, randomized phase II trial, which was subsequently converted to a phase III trial. Here, we present the results of the phase II proportion, focusing on surgical pathology and safety outcomes on an exploratory basis. Patients with resectable EGA (≥cT2 or cN+) were assigned to either four preoperative and postoperative cycles of FLOT combined with ATZ, followed by eight cycles of ATZ maintenance (arm A) or FLOT alone (arm B).

RESULTS

Two hundred ninety-five patients were randomly assigned (A, 146; B, 149) with balanced baseline characteristics between arms. Twenty-three patients (8%) had tumors with microsatellite instability (MSI), and 58% patients had tumors with a PD-L1 combined positive score (CPS) of ≥1. Surgical morbidity (A, 45%; B, 42%) and 60-day mortality (A, 3%; B, 2%) were comparable between arms. Downstaging favored arm A versus arm B (ypT0, 23% v 15% [one-sided P = .044]; ypT0-T2, 61% v 48% [one-sided P = .015]; ypN0, 68% v 54% [one-sided P = .012]). Histopathologic complete regression rates (pathologic complete response or TRG1a) were higher after FLOT plus ATZ (A, 24%; B, 15%; one-sided P = .032), and the difference was more pronounced in the PD-L1 CPS ≥10 (A, 33%; B, 12%) and MSI (A, 63%; B, 27%) subpopulations. Complete margin-free (R0) resection rates were relatively high in both arms (A, 96%; B, 95%). The incidence and severity of adverse events were similar in both groups.

CONCLUSION

Within the limitations of the exploratory nature of the data, the addition of ATZ to perioperative FLOT is safe and improved postoperative stage and histopathologic regression.
Gift of Truth
Authors: Hellmann Ilana
Published: November 2023

When our patients have terminal disease how much should we tell our patients and how should we tell them? Knowing how much to say to each of our patients, and choosing the appropriate words, is an art. The task entrusted to physicians of giving bad news is both an immense privilege and a grave responsibility.