bluuebunny/crossref_metadata_2025 huggingface dataset:
Rauwolfia vomitoria extract suppresses benign prostatic hyperplasia by inducing autophagic apoptosis through endoplasmic reticulum stress
Authors: Huang Guifang , He Xiao , Xue Zesheng , Long Yiming , Liu Jiakuan , Cai Jinming , Tang Pengfei , Han Bangmin , Shen Bing , Huang Ruimin , Yan Jun
Published: May 2022

Background

The current drug treatments for benign prostatic hyperplasia (BPH) have negative side effects. Therefore, it is important to find effective alternative therapies with significantly fewer side effects. Our previous study revealed that Rauwolfia vomitoria (RWF) root bark extract reversed BPH development in a rat model. However, the molecular mechanism of its inhibitory effects on BPH remains largely unknown.

Methods

BPH-1 and WPMY-1 cell lines derived from BPH epithelial and prostatic stromal compartments were selected to investigate how RWF extract inhibits BPH in vitro by MTT and flow cytometry assays. Microarray, quantitative real-time PCR, immunoblotting, and GFP-LC3 immunofluorescence assays were performed to evaluate the effects of RWF extract on endoplasmic reticulum stress (ER stress) and autophagic apoptosis pathways in two cell lines. A human BPH ex vivo explant assay was also employed for validation.

Results

RWF extract treatment decreased cell viability and induced apoptotic cell death in both BPH-1 and WPMY-1 cells in a concentration-dependent manner with the increase of pro-apoptotic PCDC4 protein. RWF extract induced autophagy by enhancing the levels of autophagic genes (ULK2 and SQSTM1/p62) and the LC3II:LC3I ratio, with the increase of GFP-LC3 puncta. Moreover, RWF extract activated PERK- and ATF6-associated ER stress pathways by inducing the transcriptional levels of EIF2AK3/PERK, DDIT3/CHOP and ATF6, accompanied by the reduction of BiP protein level, but not its mRNA level. Another ER stress pathway was not induced by RWF extract, as manifested by the lack of XBP1 splicing. Pharmacological inhibition of autophagy by 3-methyladenine abrogated apoptosis but not ER stress; while inhibition of ER stress by 4-phenylbutyrate alleviated the induction of autophagy and apoptosis. In addition, pretreatments with either 3-methyladenine or 4-phenylbutyrate suppressed RWF extract-induced cytotoxicity. Notably, the inductions of PERK- and ATF6-related stress pathways and autophagic apoptosis were confirmed in a human BPH ex vivo explant.

Conclusions

Our data have demonstrated that RWF extract significantly suppressed the viabilities of BPH epithelial cells and BPH myofibroblasts by inducing apoptosis via upregulating ER stress and autophagy. These data indicate that RWF extract is a potential novel alternative therapeutic approach for BPH.
Multidisciplinary blended learning to build a breast cancer specialist career: survey on the perspective of the first 2 cohorts of the ESO-ULM Certificate of Competence in Breast cancer (CCB)
Authors: Meani Francesco , Kovacs Tibor , Wandschneider Wiebke , Costa Alberto , Pagani Olivia
Published: May 2022

Background

Breast Cancer (BC) specialists need to acquire comprehensive knowledge, covering their own specialty and principles of related disciplines. Blended learning, the integration of online and face-to-face learning, is becoming more and more important in academic education and has added value during pandemics which limit face-to-face learning and residential training.

In this context, the ESO-ULM Certificate of Competence in Breast Cancer (CCB) provides postgraduate multidisciplinary education and delivers an academic postgraduate title.

The aim of this work is to investigate the degree of satisfaction of 42 participants to the first two editions of the programme and to assess if attending the programme entailed any professional gain.

Methods

An ad-hoc questionnaire was developed exploring 4 areas: participants’ characteristics, administrative aspects, CCB Program syllabus and design, professional impact.

Results

The program was attractive for specialists of different disciplines from all over the world: > 90% of responders appreciated the curriculum set up and the quality of the teaching.

Despite 64% of responders changed their clinical practice, only 33% could implement institutional changes. One third of the participants activated a collaboration with other colleagues and 64% used the CCB as a trigger to take part in other educational activities.

Only 12% of the participants had the opportunity, after CCB, to visit other BC Units or to be involved in international research projects.

More than half of the attendees profited from attending CCB in terms of promotions (16.7%), change of working institution (9.5%) or development of a more structured educational program at their home institutions (28.6%).

Conclusions

Results provide interesting and stimulating considerations on the expectations and needs of training physicians and on what modern educational tools and formats can achieve. This paper can provide useful information to navigate through what the post-graduate training market is currently offering to develop a specific curriculum in modern multidisciplinary BC care but might not be applicable to other fields of multidisciplinary oncology.
Does it make sense to refreeze ovarian tissue after unexpected occurrence of endometriosis when transplanting the tissue?
Authors: Dietl Anna K. , Dittrich Ralf , Hoffmann Inge , Denschlag Dominik , Hanjalic-Beck Aida , Müller Andreas , Beckmann Matthias W. , Lotz Laura
Published: May 2022

Background

Ovarian insufficiency is a major concern for long-term cancer survivors. Ovarian tissue cryopreservation for fertility preservation is an emerging technique that has proven successful over the past decade through transplantation of frozen-thawed ovarian tissue. Compared to other established techniques, such as oocyte freezing, ovarian tissue cryopreservation preserves actual organ function and thus the production of sex hormones. Endometriosis in perimenopausal women is rare, however it can be surprising diagnosis in the planned transplantation of cryopreserved ovarian tissue and the already thawed tissue may not be transplanted, so that it has to be refrozen.

Results

Ovarian function returned in the patient two months after transplantation, as shown by estrogen production. Ten months after the ovarian tissue transplantation mild stimulation with FSH was initiated in accordance with a low-dose protocol. When ultrasonography revealed a follicle 17 mm in size in the ovarian graft, hCG was added and after follicular puncture one oocyte was obtained. The oocyte could be fertilized by IVF and transferred to the uterus. On day 14 after embryo-transfer, a positive hCG-Level was detected and after an uncomplicated pregnancy a healthy child was delivered.

Conclusions

We report the first pregnancy and live birth achieved using transplantation of thawed and refrozen ovarian tissue in a woman treated by chemotherapy and subsequent endometriosis surgery. Refreezing of cryopreserved ovarian tissue is not a hindrance to successful transplantation of ovarian tissue. Against the background of increasing numbers of candidates for transplantation of ovarian tissue is expected that the combination chemotherapy followed by endometriosis will increase.
Effects of fixed versus variable task prioritization during short-term dual task practice on motor and cognitive task performance in young adults
Authors: Muehlbauer Thomas , Voigt Hagen , Brueckner Dennis , Beurskens Rainer
Published: May 2022

Objective

It has been shown that variable compared to fixed task prioritization during dual task practice more effectively improves motor (i.e., postural control) and cognitive (i.e., memory) performance in older adults. However, it is unclear whether this finding is also valid in young adults. Thus, the present study examined the effect of fixed (allocate equal priority on both tasks) versus variable (vary priority between both tasks) priority during short-term motor-cognitive dual task practice on single and dual task performance in healthy young adults (age range: 20–30 years).

Results

During two days of practice, significant improvements of motor (i.e., balance task: reduced root mean square error; p < 001, ηp2 = .72) and cognitive (i.e., arithmetic task: increased serial three subtractions; p < .001, ηp2 = .78) task performance were observed and that was irrespective of group (“fixed priority” and “variable priority”). Further, the statistical analysis of post-practice single and dual task performance revealed no significant differences between groups, irrespective of task (i.e., motor or cognitive). This indicates that in young as opposed to old adults, single and dual task performance improvements are independent of task prioritization (i.e., fixed or variable priority) during short-term motor-cognitive dual task practice.
Cross-species single-cell transcriptomic analysis reveals divergence of cell composition and functions in mammalian ileum epithelium
Authors: Li Haonan , Wang Xiaodan , Wang Yalong , Zhang Mengxian , Hong Fan , Wang Hong , Cui Along , Zhao Jianguo , Ji Weizhi , Chen Ye-Guang
Published: May 2022

Animal models are widely used for biomedical studies and drug evaluation. The small intestine plays key roles in nutrient absorption, hormone secretion, microbiota defense and drug absorption and metabolism. Although the intestinal structure of mammals is conserved, the differences on epithelial cell composition, functional assignments and drug absorption among mammals are largely unknown. Here, cross-species analysis of single-cell transcriptomic atlas of the ileum epithelium from mouse, rat, pig, macaque and human reveals the conserved and differential cell types and functions among species, identifies a new CA7+ cell type in pig, macaque and human ileum, uncovers the distinct expression pattern in enterocytes, enteroendocrine cells and Paneth cells, and defines the conserved and species-specific intestinal stem cell signature genes. The examination of drug absorption across species suggests that drug metabolism in mouse ileum is closer to human while drug transport in macaque ileum is more similar to human. Together, our data provide the comprehensive information about cell composition and functional assignments in five species, and offer the valuable guidance for animal model selection and drug testing.
The psychological processes of classic psychedelics in the treatment of depression: a systematic review protocol
Authors: Johansen Lauren , Liknaitzky Paul , Nedeljkovic Maja , Mastin-Purcell Lisa , Murray Greg
Published: May 2022

Background

There is currently renewed interest in the use of psychedelic therapy in the treatment of psychiatric disorders, including depression. The proposed systematic review will aim to identify, evaluate and summarise the psychological processes of change underlying psychedelic therapy for depression in the current literature and consider the implications these processes may have on the psychotherapy component of treatment.

Methods

Scopus, PsycINFO, PubMed and Web of Science databases will be searched using relevant terms. Studies will be included if they discuss the use of a classic psychedelic to treat depression symptomology in an adult population and report or propose psychological processes responsible for depression symptom change. Two authors will independently screen articles, complete quality assessment tools and conduct data extraction. Empirical and non-empirical research will be extracted and synthesised separately. A narrative synthesis approach will be used to report psychological processes identified in the literature.

Discussion

This systematic review will be the first to collate available evidence on the psychological processes associated with psychedelic therapy for depression. The preliminary nature of this research field is expected to result in the review having several limitations, namely heterogeneity between studies and the inclusion of limited empirical research. We intend for this review to present the current state of the literature, identify gaps and generate candidate variables that warrant further investigation.

Systematic review

PROSPERO CRD42020197202
Restrictive type and infectious complications might predict nadir hematological values among individuals with anorexia nervosa during the refeeding period: a retrospective study
Authors: Funayama Michitaka , Koreki Akihiro , Mimura Yu , Takata Taketo , Ogino Satoyuki , Kurose Shin , Shimizu Yusuke , Kudo Shun
Published: May 2022

Background

Although hematological abnormalities in patients with anorexia nervosa have been documented, the mechanisms involved have not been fully clarified, especially during the refeeding period when hematological values further decrease after admission prior to improving. Here we address potential mechanisms underlying the hematological abnormalities of inpatients with anorexia nervosa during the refeeding period.

Methods

We recruited patients from 101 admissions corresponding to 55 individual patients with anorexia nervosa with severe malnutrition (body mass index, 13.4 ± 3.4) from the neuropsychiatry unit in Ashikaga Red Cross Hospital during the period from October 1999 to March 2018. We analyzed three hematological cell measures, i.e., hemoglobin, white cell count, and platelet count, to determine their levels at admission and their lowest levels during the refeeding period and calculated the percent decrease in those values from admission to the nadir levels. We analyzed each measure using a general mixed model with explanatory variables, including data upon admission and a treatment-related indicator, i.e., energy intake.

Results

The initial hemoglobin value of 12.1 ± 2.7 g/dl decreased by 22.3% to 9.4 ± 2.5 g/dl; the initial white cell count was 5387 ± 3474/μl, which decreased by 33.6% to 3576 ± 1440/μl; the initial platelet count of 226 ± 101 × 103/μl decreased by 24.3% to 171 ± 80 × 103/μl. All nadir levels were observed during the refeeding period from the fifth to tenth day of hospitalization. Significant correlations among the three hematological cell measures, particularly at the nadir levels, were found. Of note, 41.7% of our patients who received red blood cell transfusion during hospitalization showed normal hemoglobin levels upon admission. The anorexia nervosa restrictive type was associated with a lower nadir level of white blood cell count. Infectious complications were related to a lower nadir level of hemoglobin and a greater percent decrease in hemoglobin level as well as to the need for red blood cell transfusion.

Conclusions

Nadir hematological cell measures of inpatients with anorexia nervosa might be predicted by the restrictive type and infectious complications. The anorexia nervosa restrictive type was associated with further decrease in hematological values during the refeeding period.
Insulin-like growth factor 5 associates with human Aß plaques and promotes cognitive impairment
Authors: Rauskolb Stefanie , Andreska Thomas , Fries Sophie , von Collenberg Cora Ruedt , Blum Robert , Monoranu Camelia-Maria , Villmann Carmen , Sendtner Michael
Published: May 2022

Risk factors such as dysregulation of Insulin-like growth factor (IGF) signaling have been linked to Alzheimer’s disease. Here we show that Insulin-like Growth Factor Binding Protein 5 (Igfbp5), an inhibitory binding protein for insulin-like growth factor 1 (Igf-1) accumulates in hippocampal pyramidal neurons and in amyloid plaques in brains of Alzheimer patients. We investigated the pathogenic relevance of this finding with transgenic mice overexpressing Igfbp5 in pyramidal neurons of the brain. Neuronal overexpression of Igfbp5 prevents the training-induced increase of hippocampal and cortical Bdnf expression and reduces the effects of exercise on memory retention, but not on learning acquisition. Hence, elevated IGFBP5 expression could be responsible for some of the early cognitive deficits that occur during the course of Alzheimer’s disease.
Pediatric metanephric adenoma with Fanconi–Bickel syndrome: a case report and review of literature
Authors: Sarhan Osama M. , Al Farhan Ahmed , Abdallah Salma , Al Ghwanmah Hamzah , Boqari Deena , Omar Helmy , Al Faddagh Abdulmohsin , Al Kanani Hanan , Al Kawai Fouad
Published: May 2022

Background

Metanephric adenoma (MA) is a rare benign renal tumor that resembles renal cell carcinoma and Wilms’ tumor in radiological as well as pathological appearance. It can present at any age or gender, and it is extremely rare in the pediatric age group with less than 50 reported cases. Fanconi–Bickel syndrome (FBS) is a rare autosomal recessive disorder of carbohydrate metabolism. Herein, we report a rare incidence of MA in a boy with a genetically confirmed FBS who underwent a nephron-sparing surgery.

Case presentation

A 21-month-old boy was referred to the pediatric urology clinic for further evaluation of an incidentally discovered left renal mass. His laboratory investigations showed normal renal function, hypophosphatemia, high blood glucose level, markedly elevated serum alkaline phosphatase, and low serum vitamin D. Blood picture showed signs of polycythemia and urinalysis showed glucosuria and aminoaciduria. Genetic testing was positive for Fanconi–Bickel syndrome. Radiological investigations were carried out with abdominal ultrasound and computerized tomography (CT) with intravenous contrast documented a sharply marginated peripheral hypoechoic hypovascular homogeneously enhancing mass at the upper pole of the left kidney measuring 2.0 × 1.8 × 2.0 cm. The child was admitted and started on supportive treatment until his medical condition was stabilized, then underwent elective open left partial nephrectomy via a left upper transverse abdominal transperitoneal incision. The excised renal mass was sent for histopathological assessment and was found to be a tumor composed of tightly packed tubules with no mitotic figures or necrosis and scanty cytoplasm consistent with MA. After good hydration and tumor resection, his polycythemia gradually improved. The patient was discharged home in a good condition with his proper replacement therapies. His follow-up abdominal ultrasound after 12 months showed no signs of recurrence.

Conclusions

Metanephric adenoma is extremely rare in the pediatric age group, especially in those who have a FBS. The only way to diagnose and treat this tumor is by surgical resection as most patients are asymptomatic. A nephron-sparing surgery is better for this age group in which the future renal function is considered.
The role of gilts in transmission dynamics of swine influenza virus and impacts of vaccination strategies and quarantine management
Authors: Ryt-Hansen Pia , Nielsen Henriette Guldberg , Sørensen Simon Smed , Larsen Inge , Kristensen Charlotte Sonne , Larsen Lars Erik
Published: May 2022

Background

Along with an expanding global swine production, the commercial housing and management of swine herds, provide an optimal environment for constant circulation of swine influenza virus (swIAV), thereby challenging farmers and veterinarian in determining optimal control measures. The aim of this study was to investigate the role of gilts in the swIAV transmission dynamics, and to evaluate the impact of different control measures such as quarantine and gilt vaccination.

Methods

The study was conducted as a cross-sectional study in ten Danish sow herds, including five swIAV vaccinated and five unvaccinated herds. Blood- and nasal swab samples of gilts, first parity sows and their piglets were collected at different stages in the production system (quarantine in/out, mating, gestation and farrowing) and analyzed for the presence of swIAV and swIAV antibodies. Associations between the detection of swIAV, seroprevalence, antibody levels, sow and gilt vaccination strategy and quarantine biosecurity were thereafter investigated to identify possible risk factors for swIAV introductions and persistence within the herds.

Results

Nine of the ten herds of the study had swIAV circulation and swIAV was detected in the quarantine, mating- and farrowing unit. The prevalence of seropositive gilts and first parity sows was significantly higher in the vaccinated herds, but swIAV was still present in nasal swabs from both gilts, first parity sows and piglets in these herds. Quarantine gilt vaccination and all-in/all-out management resulted in a significant reduction of swIAV positive gilts at the end of the quarantine period.

Conclusion

The results underline that herd vaccination and/or quarantine facilities are crucial to avoid swIAV introductions into sow herds.
Targeted quantitation of CFTR protein expression in vivo using immunoprecipitation & parallel reaction monitoring tandem mass spectrometry
Authors: Wang Hui , Dai Yunxiang , Clark Nicholas , Boeglin Lianne , Woo Caroline , Wooster Richard , Sun Gang , Sullivan James C.
Published: May 2022

Background

The cystic fibrosis transmembrane conductance regulator (CFTR) protein is a low-abundance membrane protein. The dysfunction of CFTR protein is the fundamental cause of cystic fibrosis (CF), a fatal genetic disease. In recent years, the novel messenger RNA (mRNA)-based therapy shows high potential to treat CF disease, by delivering CFTR mRNA into lung epithelial cells to generate fully functional CFTR replacement protein. To evaluate mRNA drug efficacy, a targeted quantitative proteomics method is needed to estimate the expression level of mRNA encoded CFTR protein.

Methods

In this paper, a method combining membrane protein extraction, immunoprecipitation (IP), and nanoLC-MS/MS for quantifying CFTR in lung tissue samples was reported for the first time. Absolute quantification was performed by constructing a standard curve by spiking recombinant human CFTR protein in mouse lung tissue matrix.

Results

This method was qualified, with good linearity of standard curve and lower limit of quantification of human CFTR at 1.4 pg per mg tissue. The coefficient of variation of back calculated concentration of all standards and their back-calculation errors were < 20%. The CFTR expression level in mouse lungs dosed with mRNA encapsulated lipid nanoparticle (LNP), and the endogenous level in wild type human lungs were measured successfully.

Conclusions

The result demonstrated high sensitivity, precision and accuracy of this proteomics method for quantifying low-abundance CFTR protein in lung tissue sample.
Medicinal, nutritional, and nutraceutical potential of Sparassis crispa s. lat.: a review
Authors: Sharma Neha , Tapwal Ashwani , Verma Rachna , Kumar Dinesh , Nepovimova Eugenie , Kuca Kamil
Published: May 2022

Sparassis crispa is an edible mushroom exhibiting a wide range of medicinal properties. It is recognized for therapeutic value because of the high β-glucan content in the basidiomes. The broad range of its reported curative effects include anti-tumour, anti-cancer, immune-enhancing, hematopoietic, anti-angiogenic, anti-inflammatory, anti-diabetic, wound-healing, antioxidant, anti-coagulant, and anti-hypertensive properties. However, most of the studies are conducted on immunomodulatory and anticancer activities. Besides this, it also exhibits anti-microbial properties due to the presence of sparassol. Technology is now available for the cultivation of S. crispa on coniferous sawdust. This review is an attempt to focus on its distribution, taxonomy, chemical composition, medicinal properties, potential applications, and artificial cultivation.
Toll-like receptor 10 gene polymorphism and risk of multiple sclerosis among Iraqi patients
Authors: Atiyah Noor S. , Fadhil Hula Y. , Ad’hiah Ali H.
Published: May 2022

Background

Toll-like receptors (TLRs) are a family of 10 pattern recognition receptors (TLR1–TLR10) involved in the regulation of inflammatory and immune responses besides their role in the pathogenesis of autoimmune diseases including multiple sclerosis (MS). TLR10 is the least studied TLR in MS, and data for single nucleotide polymorphisms (SNPs) of the TLR10 gene are limited. Therefore, a case–control study was performed on 85 patients with relapsing–remitting MS and 86 healthy controls (HC) to explore SNPs in the promoter region of TLR10 gene. A 927-bp region was amplified, and Sanger sequencing identified 10 SNPs with a minor allele frequency ≥ 10% (rs200395112 T/A, rs201802754 A/T, rs201228097 T/A, rs113588825 G/A, rs10004195 T/A, rs10034903 C/G, rs10012016 G/A/C, rs10012017 G/T, rs33994884 T/Deletion [Del] and rs28393318 A/G).

Results

Del allele and T/Del genotype of rs33994884, as well as AG genotype of rs28393318, showed significantly lower frequencies in MS patients compared to HC. Allele and genotype frequencies of the 10 SNPs showed no significant differences between MS patients classified according to the Expanded Disability Status Scale. Haplotype analysis revealed that haplotype A-T-A-G-A-G-G-T-A showed a significantly increased frequency in MS patients compared to HC (odds ratio [OR] = 9.70; 95% confidence interval [CI] = 1.28–73.31; corrected probability [pc] = 0.03), while frequency of A-T-A-G-T-C-A-T-G haplotype was significantly decreased (OR = 0.10; 95% CI = 0.01–0.85; pc = 0.05).

Conclusions

The study indicated that two SNPs may influence susceptibility to MS (rs33994884 and rs28393318), but haplotype analysis of TLR10 gene SNPs was more informative.
Value of teff (Eragrostis tef) genetic resources to support breeding for conventional and smallholder farming: a review
Authors: Woldeyohannes Aemiro Bezabih , Desta Ermias Abate , Fadda Carlo , Pè Mario Enrico , Dell’Acqua Matteo
Published: May 2022

Crop germplasm collections are a key asset to support the resilience and productivity of cropping systems worldwide. In their diversity lays an oftentimes untapped reservoir of alleles that may enable breeding strategies targeting local adaptation, resulting in enhanced performance and higher varietal uptake. In the past five decades, the national genebank of Ethiopia actively collected and conserved thousands of teff (Eragrostis tef) accessions, a staple crop throughout the Horn of Africa at the basis of countless cultural uses and with high market relevance. This review article emphasizes the breeding significance of teff genetic resources, highlighting current challenges in teff farming and improvement that could be addressed further valorising germplasm collections. We collect data generated on the largest teff ex situ collections in the world to discuss opportunities to improve teff tolerance to stress and lodging, as well as to increase its productivity across its cropping area. In doing so, we highlight and critically revise current and past literature tapping in teff diversity to support teff improvement. This review starts providing a summary of teff characteristics, detailing the status and challenges of teff cultivation and breeding. It then follows describing the diversity existing in teff diversity collections and its relevance for teff improvement. The review concludes describing the molecular studies undertook on teff in the past two decades, highlighting the perspectives of molecular breeding for teff. The body of knowledge available on teff shows that there is large potential for improvement of this crop to target smallholder farming systems as well as international markets, and that improvement may start from the large diversity available in teff collections.
3D magnetic characterization of the Aimorés structure (Brazil) aiming to identify interpretation elements under cover: Impact crater or circular intrusion?
Authors: de Oliveira Maria José Campos , Melo Aline Tavares , Vasconcelos Marcos Alberto Rodrigues
Published: May 2022

The Aimorés intrusive complex (AIC), located in the Araçuaí belt (Brazil), has been characterized for many years as the Aimorés Impact Crater due to its topographic features, such as the circular morphology and the ring-shaped rim. Detailed geologic mapping finds a zoned igneous intrusion composed of granite and charnockite rocks in the outer rims, whereas the central part of the structure is covered by overburden. In the absence of direct evidence under the center of the structure, uncertainty remains and there is ambiguity about the geologic interpretation of the area. For this reason, we have used magnetic data to investigate the AIC structure in the subsurface. We explore the different possibilities of geologic scenarios for this region, namely, a pluton with eroded center, a zoned intrusion, a simple impact crater, and a complex impact crater through a synthetic study. Our synthetic tests revealed zoned intrusion and simple impact crater as possible geologic scenarios. Then, in the next stage, we characterize the AIC in three dimensions to unveil the subsurface geometry of the magnetic rocks. The inverted model found the geometry of a high susceptibility ring-shaped body that extends at 4 km depth, pointing to a circular zoned intrusion as the more likely interpretation. Our study has revealed two new geologic features in the study area: (1) the presence of two distinct zones under the central depression cover of the AIC and (2) a new zoned body at southeast of the AIC, which has not been mapped previously because of the overburden. We find the efficacy of using magnetic data for mapping postcollisional intrusions potentially associated with lithium mineralization in subsurface.
Pathologic Characteristics of Patients in the Kamuzu Central Hospital Lymphoma Study (2013-2019)
Authors: Dewey Morgan , Lilly Amy , Painschab Matthew , Tomoka Tamiwe , Fedoriw Yuri
Published: May 2022

PURPOSE

We evaluated the concordance of lymphoproliferative disorder (LPD) diagnoses made initially at Kamuzu Central Hospital (KCH) with a limited immunohistochemistry panel and telepathology consultation with University of North Carolina (UNC) at Chapel Hill and second review at UNC with an extensive immunohistochemistry panel available.

METHODS

The prospective KCH Lymphoma Study in Lilongwe has been enrolling patients with LPDs since 2013. Diagnoses are made by pathologists in Malawi and supported by US pathologists and Malawian clinicians at weekly telepathology conferences. Diagnostic tissue blocks are sent quarterly to UNC for secondary review and further confirmatory studies. Concordance of diagnosis from primary to secondary review was scored as: exact match (level 1), differences in granularity of the diagnosis (level 2), a change in classification but not in treatment (level 3), and a change to the diagnosis that would have altered the treatment course (Major Discordance). Cases with insufficient tissue for review at UNC were excluded from concordance evaluation.

RESULTS

Three hundred eighty-eight adult patients were enrolled (June 2013-May 2019). Three hundred twenty-seven tissue blocks were sent to UNC for review and 292 LPDs diagnostic samples had sufficient quality for concordance review. The five most common LPDs were diffuse large B-cell lymphoma (n = 143, 49%), Burkitt lymphoma (9%, n = 25, 8%), classical Hodgkin lymphoma (8%, n = 23), Multicentric Castleman disease (8%, n = 23), and low grade non-Hodgkin lymphoma (6%, n = 17). Level 1, 2 and 3 concordance represented 175 (60%), 49 (17%) and 50 (17%) cases, respectively, and a Major Discordance was identified in 18 cases (6%).

CONCLUSION

With a limited, selected immunohistochemistry panel and telepathology consultation, 94% of cases were accurately classified in real-time, leading to appropriate therapy. The evaluation of concordance provides a measure of quality assurance of the telepathology program, confidence in diagnoses for involvement in interventional trials, and useful data for understanding the epidemiology of LPDs in Malawi.
Characterizing Geospatial Access and Potential Barriers for Women Presenting With Breast Concerns to Bugando Medical Center in Mwanza, Tanzania
Authors: Friebel-Klingner Tara , Joo Emma , Kirahi Matagoro , Masalu Nestory , Washington Leonard , Rositch Anne
Published: May 2022

PURPOSE

In Tanzania, high breast cancer morbidity and mortality can be attributed in part to delays due to poor access to comprehensive cancer services. Bugando Medical Center (BMC) is one of four tertiary care hospitals in Tanzania. We aimed to describe the catchment area and potential barriers to access for women presenting to BMC with breast concerns.

METHODS

This prospective cohort included women presenting to BMC between September 2019 and January 2021. Patients were geocoded to residential regions and a presentation rate (PR) for each region was calculated using the number of presenting patients per at-risk female population. The main travel route from each region's referral hospital to BMC was determined using Google maps. We used descriptive statistics to depict geospatial, demographic, and clinical variables.

RESULTS

The catchment area included 10.5 million women from eight regions in the Lake Zone of Tanzania. We studied 547 patients aged 18-87 (mean: 44.3), 35% (n = 196) had health insurance, and mean PR was 5.26 per 100,000 women (range: 2.01-13.86). Median distance to BMC was 121 km (IQR: 3-247) and 18% of patients likely required a ferry. As distance increased, PR tended to decrease. PRs were lower for three regions where a ferry was indicated for travel (2.01, 2.32 and 3.06). There were 151 (28%) patients diagnosed with breast cancer, with a mean breast cancer PR of 1.45 per 100,000 women (range: 0.64-3.12). The proportion of breast cancers diagnosed increased with increasing travel distance. Additionally, 51 (26%) breast cancer patients were lost to follow up without any treatment.

CONCLUSION

BMC has a large geographic catchment area comprised of eight regions, all with low breast cancer PR. Our findings indicate that burdensome geographic access to cancer care, lack of health insurance, and lost to follow-up, are likely contributing to the high breast cancer mortality in Tanzania.
Stronger Together Toolkit: An Open Resource to Implement Evidence-Based Peer-to-Peer Support Programs for Cancer Patients Globally
Authors: Taylor Carolyn , Cabanes Anna , Le Phuongthao , Afifi Sarah
Published: May 2022

PURPOSE

The global burden of cancer falls heavily on low-and middle-income countries (LMICs), where there are critical gaps in the provision of supportive care. Initiatives to translate effective, resource-appropriate preventions and clinical treatments in LMICs have been gathering pace, yet few examples exist to guide the translation of interventions that address the high unmet psychosocial needs among cancer patients. To address this gap, we have recently published a theory-based cultural adaptation of this peer mentoring program to the context of Viet Nam ( https://pubmed.ncbi.nlm.nih.gov/34365524/ ). To increase access to evidence-based supportive cancer care, building on our prior work we have developed a toolkit which provides guidance for the implementation of a culturally appropriate and resource adaptable, peer-to-peer support program.

METHODS

A multidisciplinary team of cancer experts and advocates employed a multi-step process to develop a virtual toolkit to guide the implementation of a peer-to-peer support program that coordinates with oncology centers to train and supervise cancer survivor-volunteers to assist cancer patients and their families better understand and navigate their treatment.

RESULTS

The “Stronger Together Toolkit” (STT) is an open-source, self-guided peer support program that allows for the provision of cultural and resource adaptation. STT includes six modules which use resources such as videos, slides, and worksheets, to define the intervention, engage and communicate with stakeholders, assess for readiness and plan for implementation, train program coordinators and peer mentors, evaluate training and implementation, create policies and procedures for different contexts, and identify opportunities for sustainable funding.

CONCLUSION

STT can be used to increase access to supportive cancer care in a way that ensures that the program and activities are acceptable and appropriate to the culture, health system, and resources of the local community and setting. In addition, the STT can be adapted to introduce peer to peer support across additional disease platforms.
Exploring Barriers and Facilitators for Cervical Cancer Screening in Iquitos, Peru: Application of the COM-B Behavior Model to Inform Program Implementation
Authors: Correa-Mendez Margarita , Paz-Soldan Valerie , Blechter Batel , Gravitt Patti E. , Rositch Anne F. , Meza Graciela
Published: May 2022

PURPOSE

Cervical cancer is the second cause of death among Peruvian women. In Iquitos, Proyecto Precancer engages key stakeholders to develop interventions that address women's needs and prevent cervical cancer. Successful prevention programs rely on behavior change interventions that must be supported by a theoretical understanding of the behavior. The Capability, Opportunity, Motivation, Behavior (COM-B) model informs what must be modified for a behavior change intervention to be effective.

METHODS

A cervical cancer prevention focused Knowledge-Attitudes-Practices (KAP) survey was administered in 2017 to women ages 18-65 years living in Iquitos, Peru using census-based random sampling. To identify context-specific barriers and facilitators for cervical cancer screening in Iquitos, we mapped KAP survey data onto key themes in the COM-B model.

RESULTS

Out of 619 women, 67.9% had been screened for cervical cancer at least once. Facilitators to screening-seeking behaviors were having the knowledge about cervical cancer (80.5% of women), partner support (74.8%), attending a health post (79.5%) and receiving information from a health post (63.6%). Among women not previously screened, fear was the primary barrier (41.7%). Perceived risk of cervical cancer was high (79.1%) but experiencing symptoms as a reason to seek screening remains a common misconception (36%).

CONCLUSION

Behavior change interventions must address the sources of fear and raise awareness about seeking cervical cancer screening prior to symptom development. Focusing on health posts and partners as key facilitators could help improve the outcomes of programs implemented by Proyecto Precancer in Iquitos.
Training for Primary Care Providers: Case Study From Rwandan Cervical Cancer Educate, Screen, and Treat (EST) Program
Authors: Weber Callie , Graef Katy , Hagenimana Marc , Mwiza Elisabeth , Kuteesa Justine , Uwamariya Therese , Broadwin Cassandra , Davidson Heather , Rutagengwa William
Published: May 2022

PURPOSE

Cervical cancer screening, triage, and treatment programs are expanding across Rwanda's districts. Screening for cervical cancer is needed at the local level, but health center nurses and midwives in the Bugesera district have not received formalized training.

METHODS

The RBC-BVGH Cervical Cancer Educate, Screen, and Treat (EST) Program introduced services in Bugesera district for the first time. In 4-week EST campaign (September 6-October 1], 4,013 women were screened for HPV, 2,056 for VIA, 282 received same-day TA, nine were treated with LEEP at Nyamata DH, and 26 were referred to a Kigali tertiary hospital (Rwanda Military Hospital; RMH) with suspected cervical cancer. Prior to launch of services, providers from 16 health facilities received training (52 nurses/midwives, 17 data managers, 15 lab technicians). The quality and sustainability impact of the training was determined through a pre- and post- course theory assessment (N = 52) and a post-EST survey (N = 15). On the post-EST survey, providers self-ranked their skill confidence across each service before vs. after the campaign on 5-point Likert scale (1 = low and 5 = high).

RESULTS

Following the training program, participants' cervical and breast cancer assessment scores increased by an average of 949% and 405% respectively ( P < .001). The participants' self-reported confidence in the following techniques also increased: HPV sample collection (206%), visual inspection with acetic acid (187%), thermal ablation (205%), breast examination (54%), and referral of cervical cancer cases (57%). One hundred percent of participants indicated their intent to apply the program learnings in their daily practice yet noted that a refresher training within 3-9 months would be valued.

CONCLUSION

The above results demonstrate that RBC's training programs effectively provide strong theoretical and hands-on training for primary providers. Continued mentorship and refresher trainings are critical for sustainability of high-quality cervical and breast cancer screening, triage, and treatment services in Rwanda.
Presenting Symptoms and Stage at Diagnosis Among Women Diagnosed With Breast Cancer Through a Combined Breast Cancer and Cervical Cancer Screening Program in Rwanda
Authors: Pace Lydia , Vianney Dusengimana Jean-Marie , Balinda Jean Paul , Benewe Marie Origene , Rugema Vestine , de Dieu Uwihaye Jean , Fata Amanda , Shyirambere Cyprien , Shulman Lawrence , Keating Nancy , Uwinkindi Francois , Hagenimana Marc
Published: May 2022

PURPOSE

There is interest in leveraging cervical cancer (CC) screening to facilitate early breast cancer (BC) detection in low- and middle-income countries (LMIC). We sought to determine whether adding clinical breast exams (CBE) to CC screening led to early BC diagnoses among asymptomatic women in Rwanda's Women's Cancer Early Detection Program (WCEDP). The WCEDP provided CBE to women aged 30-49 who were receiving CC screening, as well as any individual with breast symptoms.

METHODS

The WCEDP was launched in three Rwandan districts (total population 1.3 million) in July 2018, August 2018 and May 2019 respectively. This analysis included patients presenting to health centers (HCs) through December 31, 2019. Follow-up data were collected through April 2021 using clinicians' weekly reports, patient navigator referral data, and the cancer hospital's electronic medical record. We determined patients' initial symptoms from HC records, patient interviews, and phone surveys.

RESULTS

Nine thousand seven hundred sixty-three women received CC screening and CBE together; 7,616 additional women received CBE alone. Five hundred eighty-five women were referred from HCs to a district hospital (DH) for abnormal CBE; 200 were referred from the DH to the referral hospital. Twenty-nine women were diagnosed with BC; of these 19 (66%) were 50 or older and 23 (79%) had stage III/IV disease. Median interval from HC visit to referral hospital visit was 19 days (IQR 11.0-26.0). Among the 23 women with BC for whom we could identify their reason for initial HC presentation, all had sought care for breast symptoms. The remaining six had advanced-stage disease and symptomatic tumors at diagnosis.

CONCLUSION

During the initial rollout of this combined BC and CC screening program, no BC was diagnosed among asymptomatic women and 2/3 women diagnosed with BC were older than the target CC screening age. Adding CBE for all women receiving CC screening in LMIC may be low-yield. Given the high proportion of late-stage diagnoses, community awareness of early BC symptoms, high-quality CBE and timely referrals are important areas of focus.
Impact of Inperson Training on Health Care Provider Knowledge of the Symptoms and Treatment of Pediatric Cancer in Mwanza Region
Authors: Mtenga Norbert , Nnko Glorian , Nchasi Goodluck , Magese Eric , Rajabu Shabani , Sued Hillary , Joas Heronima , Sanga Erica , Schroeder Kristin
Published: May 2022

PURPOSE

In Tanzania, < 20% of the estimated 3,500 children who develop cancer each year present to one of the three cancer treatment centers. Of those who do present, there is an average of 89 days between when they present to the local health care center and their cancer center evaluation. Our aim was to assess the baseline pediatric cancer knowledge among medical providers at health centers and district hospitals in the Mwanza region and evaluate the impact of a training program on cancer knowledge and symptom recognition, and ultimately reduce referral delay.

METHODS

One provider from each of the 69 Mwanza region health care centers and district hospitals was selected by district non communicable disease coordinators to participate in a one day training program. Training education strategies included didactic, small group discussions and interactive sampling. Topics included childhood cancer epidemiology, symptoms recognition, diagnostic evaluation, and referral options. Participants completed re- and post-training surveys to determine knowledge change.

RESULTS

A total of 80% (n = 56) of invited health centers participated in the training. In the pre survey, while all participants knew what cancer was (uncontrolled cellular division), 82% of were not aware that there was potentially curative treatment available, and 35% did not know which hospitals provided cancer treatment in their region. Post training, overall knowledge scores significantly increased (73%-81%, P < .001), with a > 20% score change for key content areas including symptom recognition and appropriate referral location hospital.

CONCLUSION

Community medical provider knowledge about childhood cancer is low within the Mwanza Region. In person short training is an effective strategy to increase key knowledge areas that are known to contribute to referral delay. Future research will evaluate the impact of this training on referral rates and referral delay to the regional cancer referral hospital.
Urban and Rural Patients Perspectives on Late Diagnosis of Breast Cancer in Tanzania: A Qualitative Study
Authors: Msoka Elizabeth F. , Cyril Perry M. , Serventi Furaha , Kitali Brenda C. , Saria Vivian F. , Masenga Gilleard G. , Mmbaga Blandina T. , Gutnik Lily
Published: May 2022

PURPOSE

In Tanzania, women are diagnosed at an advanced stages of breast cancer. The aim of this study is to identify reasons for this finding from the patient perspective.

METHODS

Semi-structured in-depth interviews were conducted in inpatient and outpatient settings in the Kilimanjaro Cancer Care Center. Thematic coding via grounded theory technique was done by two independent reviewers.

RESULTS

Ten 10 patients (five rural and five urban) participated in the study. The average ages was 48. Seven (70.0%) were Christian. Eight (80.0%) patients had primary education, six (60.0%) were married, and eight (80.0%) were not employed. Two women (20.0%) had stage 2, four women (40.0%) had stage 3, and 4 (40.0%) had stage 4. The most common reasons reported by patients for advanced stage breast cancer at time of diagnosis are initially seeking care from traditional healers (n = 6, 60.0%), lack of breast cancer sign and symptoms knowledge (n = 8, 80.0%), misconceptions about breast cancer treatment especially mastectomy (n = 5, 50.0%), distrust of conventional medicine (n = 4, 40.0, seeking support from the religious leaders (n = 6, 60.0%). Furthermore, we found that, almost all (n = 9, 90.0%) of the patients express their concern regarding financial challenges to access care and treatment for cancer. For example (n = 3, 30.0%) said payment for cancer treatment is too costly and six patients (60.0%) stated that lack of money for transportation.

CONCLUSION

Lack of adequate breast cancer knowledge and awareness, patient provider relationships, and access to care are the most common mentioned reasons for advanced disease at time of diagnose among breast cancer patients. Engagement with the community through cultural sensitive public health campaigns and interventions must be designed to alleviate the misconceptions and knowledge gap in these communities. System level change is needed to improve access to care.
Disclosure by Design
Authors: Pandya Mihir
Published: May 2022

This essay revisits the saga of Cold War era stealth development programs—classified but curiously public efforts to build airplanes that eluded radar detection—to explore how leaks work and the work leaks do when designing complex technical systems. Stealth programs are aging examples of an increasingly visible phenomenon: disclosures about large, closely guarded design, manufacturing, and administrative efforts before their official unveiling. Rather than simply policing the boundary between the secret and the public, in “big” design, in collective efforts to produce knowledge and things at scale, the article argues that leaks have a more subtle purpose: they help govern the uncertain terrain between knowing and knowing enough.