bluuebunny/crossref_metadata_2025 huggingface dataset:
Emergency Department Visits in the Year Prior to Total Shoulder Arthroplasty as a Risk Factor for Postoperative Emergency Department Visits
Authors: Werner Brian C. , Bustos Francis P. , Gean Richard P. , Deasey Matthew J.
Published: March 2021

Background: Recent research has found a high rate of emergency department (ED) use after lower extremity arthroplasty; one study found a risk factor for ED presentation after lower extremity arthroplasty was presentation to the ED in the year prior to surgery. It is not known whether a similar association exists for total shoulder arthroplasty (TSA). Questions/Purposes: The goal of this study was to investigate the relationship between preoperative ED visits and postoperative ED visits after anatomic TSA. Methods: The 100% Medicare database was queried for patients who underwent anatomic TSA from 2005 to 2014. Emergency department visits within the year prior to the date of TSA were identified. Patients were additionally stratified by the number and timing of preoperative ED visits. The primary outcome measure was one or more postoperative ED visits within 90 days. A multivariate logistic regression analysis was used to control for patient demographics and comorbidities. Results: Of the 144,338 patients identified, 32,948 (22.8%) had an ED visit in the year prior to surgery. Patients with at least 1 ED visit in the year before surgery presented to the ED at a significantly higher rate than patients without preoperative ED visits (16% versus 6%). An ED visit in the year prior to TSA was the most significant risk factor for postoperative ED visits (in the multivariate analysis). The number of preoperative ED visits in the year prior to surgery demonstrated a significant dose-response relationship with increasing risk of postoperative ED visits. Conclusions: Postoperative ED visits occurred in nearly 10% of Medicare patients who underwent TSA in the period studied. More frequent presentation to the ED in the year prior to anatomic TSA was associated with increasing risk of postoperative ED visits. Future studies are needed to investigate the reasons for preoperative ED visits and if any modifiable risk factors are present to improve the ability to risk stratify and optimize patients for elective TSA.
Vertebral Fractures After Denosumab Discontinuation in Breast Cancer Survivors: A Single Institution Experience
Authors: Yeung Michele , Ho Kaylee , Fornier Monica N. , Farooki Azeez
Published: March 2021

Background: Denosumab is approved to prevent fragility fractures in patients with osteoporosis at high risk for fracture and to prevent bone loss in patients with breast and prostate cancer who receive endocrine therapy. The antiresorptive effect of denosumab rapidly dissipates when it is delayed or discontinued, but the risk for, and incidence of, multiple clinical vertebral fractures in patients with breast cancer after stopping denosumab is currently unclear. Question/Purposes: We sought to identify the incidence of clinical vertebral fractures in patients with breast cancer who received at least 2 doses of denosumab (60 mg) and then discontinued the medication. Methods: We conducted a retrospective chart review to identify patients with a history of breast cancer who were treated with denosumab between June 1, 2010, and July 18, 2018, at Memorial Sloan Kettering Cancer Center. We identified 335 postmenopausal women and 1 man with nonmetastatic breast cancer who received their final denosumab injection at least 6.5 months earlier. Data recorded included baseline bone density and the incidence of vertebral fractures after denosumab discontinuation. Results: The median age of patients was 62 years. Patients received between 2 and 13 denosumab doses before drug discontinuation. Most of the patients (310; 92.3%) were also treated with aromatase inhibitors. Of the 194 patients with baseline bone density data, 50 (25.8%) had normal bone density, 97 (50.0%) had osteopenia, and 47 (24.2%) had osteoporosis. The median follow-up duration from the last denosumab dose was 18.5 months. We identified 1 case of spontaneous vertebral fractures after denosumab stoppage. We found no cases of osteonecrosis of the jaw or atypical femur fracture. Most of the patients (88%) had a gap in denosumab dosing. Conclusions: Clinicians treating patients with breast cancer—especially those continuing to take aromatase inhibitors—should be aware of the possible risks of delaying doses of or discontinuing denosumab and should educate their patients accordingly. Prospective studies are needed to fully evaluate the risks of stopping or delaying denosumab.
High inter- and intra-observer agreement for measuring tissue oxygenation of the plantar surface of the foot in healthy participants with the Hyperview®: A pilot study
Authors: van Schilt Kaz LJ , Hollander Evert-Jan F , Veen Oscar C , Koelemay Mark J , van Geloven Anna AW , Olthof Dominique C
Published: March 2021

Objectives

The Hyperview® is a novel camera that applies hyperspectral imaging to project local concentrations of oxyhaemoglobin (OXY), deoxyhaemoglobin (DEOXY) and O2-saturation (O2-SAT) in a map. In this pilot validation study, we assessed inter - and intra-observer agreement for measuring OXY, DEOXY and O2-SAT in healthy participants.

Methods

The plantar region of the right foot was assessed with the Hyperview® in 50 healthy participants. Two consecutive pictures were taken by the same observer, followed by two images by a second observer. Measurements were performed without and with standardization (a static device for both the foot and the Hyperview camera). Inter- and intra-observer agreements were expressed as Intraclass Correlation coefficients (ICC) with their 95% confidence interval (CI). A score <0.40 indicates poor agreement, 0.40–0.59 fair, 0.60–0.74 good and 0.75–1.00 excellent agreement. Bland and Altman plots were also generated.

Results

Without standardization, the ICC values between the observers for OXY, DEOXY and O2-SAT ranged from 0.70 to 0.83. The intra-observer agreement of both observers ranged from 0.36 to 0.83. With standardization, the ICC values between the observers ranged from 0.80 to 0.82 and intra-observer agreement varied from 0.75 to 0.92. Four Bland and Altman plots were generated of the measurements of OXY by observers 1 and 2.

Conclusions

When standardization is used, the Hyperview® camera is a reliable device with excellent intra- and inter-observer agreements for the assessment of OXY, DEOXY and O2-SAT. In future research, the inter- and intra-observer agreements of the camera should be investigated in patients with diabetes and/or peripheral arterial disease.
Molecular clues in the regulation of mini‐puberty involve neuronal DNA binding transcription factor NHLH2
Authors: Hadziselimovic Faruk , Verkauskas Gilvydas , Stadler Michael B.
Published: March 2021

Gonadotropin releasing hormone agonist (GnRHa) treatment following surgery to correct cryptorchidism restores mini-puberty via endocrinological and transcriptional effects and prevents adult infertility in most cases. Several genes are important for central hypogonadotropic hypogonadism in mammals, including many that are transcribed in both the brain and testis. However, the expression of these genes in prepubertal gonads has not been studied systematically, and little is known about the effect of hormone therapy on their testicular and neuronal expression levels. In this review, we interpret histological sections, data on hormone levels, and RNA profiling data from adult normal testes compared to pre-pubertal low infertility risk (LIR) and high infertility risk (HIR) patients randomly treated with surgery in combination with GnRHa or only surgery. We organize 31 target genes relevant for idiopathic hypogonadotropic hypogonadism and cryptorchidism into five classes depending on their expression levels in HIR versus LIR samples and their response to GnRHa treatment. Nescient-helix-loop-helix 2 (NHLH2) was the only gene showing a decreased mRNA level in HIR patients and an increase after GnRHa treatment. This phenomenon may reflect a broader effect of hormone treatment on gene expression in both testicular and central nervous system tissues, which could explain why the hypothalamus-pituitary-testicular axis is permanently restored by the administration of GnRHa.
Cloning and expression analysis of GATA1 gene in Carassius auratus red var
Authors: Tian Yusu , Sun Yuandong , Ou Mi , Cui Xiaojuan , Zhou Dinggang , Che Wen’an
Published: March 2021

Background

GATA1 is a key transcription factor in the GATA family, and promotes the differentiation and maturation of red blood cell, which is essential for normal hematopoiesis.

Results

Our results showed that the cDNA sequence ofGATA1 was 2730 bp long encoding 443 amino acids. qRT-PCR analysis demonstrated thatGATA1 had the highest expression in testis (T), followed by pituitary (P) and spleen (S).GATA1 gene expression inC. auratusred var. embryo from the neuroblast stage (N) to the embryo hatching (H) changes continuously; and the gene expression levels of nonylphenol (NP)-treated and those of control embryos were significantly different. Moreover, Methylation levels ofGATA1gene in NP-treated embryos were higher than those in control embryos, indicating that NP affectedGATA1methylation.

Conclusions

Our study provides cues for further studying the roles ofGATA1 gene in fish development, and suggested a potential molecular mechanism by which NP leads to abnormal development of fish embryos.
The lung microbiota in Korean patients with non-tuberculous mycobacterial pulmonary disease
Authors: Kang Sung-Yoon , Kim Hyojung , Jung Sungwon , Lee Sang Min , Lee Sang Pyo
Published: March 2021

Background

The microbiota of the lower respiratory tract in patients with non-tuberculous mycobacterial pulmonary disease (NTM-PD) has not been fully evaluated. We explored the role of the lung microbiota in NTM-PD by analyzing protected specimen brushing (PSB) and bronchial washing samples from patients with NTM-PD obtained using a flexible bronchoscope.

Results

Bronchial washing and PSB samples from the NTM-PD group tended to have fewer OTUs and lower Chao1 richness values compared with those from the control group. In both bronchial washing and PSB samples, beta diversity was significantly lower in the NTM-PD group than in the control group (P = 2.25E-6 and P = 4.13E-4, respectively). Principal component analysis showed that the PSBs and bronchial washings exhibited similar patterns within each group but differed between the two groups. The volcano plots indicated differences in several phyla and genera between the two groups.

Conclusions

The lower respiratory tract of patients with NTM-PD has a unique microbiota distribution that is low in richness/diversity.
Body perception disturbances in women with pregnancy-related lumbopelvic pain and their role in the persistence of pain postpartum
Authors: Goossens Nina , Geraerts Inge , Vandenplas Lizelotte , Van Veldhoven Zahra , Asnong Anne , Janssens Lotte
Published: March 2021

Background

Lumbopelvic pain (LPP) is common during pregnancy and can have long-lasting negative consequences in terms of disability and reduced quality of life. Therefore, it is crucial to identify women at risk of having pregnancy-related LPP after childbirth. This study aimed to investigate the association between body perception, pain intensity, and disability in women with pregnancy-related LPP during late pregnancy and postpartum, and to study whether a disturbed body perception during late pregnancy predicted having postpartum LPP.

Methods

A prospective cohort study in 130 primiparous women (median age = 30 years) was performed. Pain intensity, disability, and lumbopelvic body perception during the last month of pregnancy and 6 weeks postpartum were assessed with the Numerical Pain Rating Scale (NPRS), Oswestry Disability Index, and Fremantle Back Awareness Questionnaire, respectively. Having pregnancy-related LPP was defined as an NPRS score ≥ 1/10. At both timepoints, women were categorized into three groups; pain-free, LPP with low disability, and LPP with high disability (based on Oswestry Disability Index scores). At each timepoint, body perception was compared between groups, and correlations between body perception, pain intensity, and disability were evaluated in women with LPP by using non-parametric tests. Logistic regression analysis was used to determine whether body perception during the last month of pregnancy predicted the presence of LPP 6 weeks postpartum.

Results

Women with LPP at the end of pregnancy, and 6 weeks postpartum reported a more disturbed body perception compared to pain-free women (p ≤ 0.005). Greater body perception disturbance correlated with higher pain intensity (σ = 0.266, p = 0.008) and disability (σ = 0.472, p < 0.001) during late pregnancy, and with pain intensity 6 weeks postpartum (σ = 0.403, p = 0.015). A disturbed body perception during late pregnancy nearly significantly predicted having postpartum LPP (Odds Ratio = 1.231, p = 0.052).

Conclusions

Body perception disturbance was greater in women experiencing LPP during late pregnancy and postpartum compared to pain-free women, and correlated with pain intensity and disability. Though non-significant (p = 0.052), the results of the regression analysis suggest that greater body perception disturbance during late pregnancy might predict having LPP postpartum. However, future studies should follow up on this.
Validity of a simple footprint assessment board for diagnosing the severity of flatfoot: a prospective cohort study
Authors: Toyooka Seikai , Shimazaki Naoya , Yasui Youichi , Ando Shuji , Saho Yasuaki , Nakagawa Takumi , Kawano Hirotaka , Miyamoto Wataru
Published: March 2021

Background

A simple, non-quantitative, and cost-effective diagnostic tool would enable the diagnosis of flatfoot without need for specialized training. A simple footprint assessment board that investigates which toe the cord passes through from the centre point of the heel to the most lateral point of the medial contour of the footprint has been developed to assess flatfoot. The purpose of this study was to verify the validity of a simple footprint assessment board for flatfoot.

Methods

Thirty-five consecutive patients with foot pain, foot injury, or any associated symptoms who underwent computed tomography (CT) were analysed prospectively. At the time of the CT scan, a footprint analysis using a simple footprint assessment board was performed. The navicular index, tibiocalcaneal angle, and calcaneal inclination angle were evaluated by CT to assess flat feet. These three criteria were compared to those evaluated with the simple footprint assessment board by regression analysis. In addition, the same analysis was conducted separately for young, middle-aged, and older patients in order to investigate each age group.

Results

The navicular index and tibiocalcaneal angle generally decreased as the score of the simple footprint assessment board increased. Calcaneal inclination angle generally increased as the score of the simple footprint assessment board increased. As the scores of the simple footprint assessment board decreased by approaching the great toe, the navicular index and tibiocalcaneal angle were higher and calcaneal inclination angle was lower, which is indicative of a higher likelihood of flatfoot. The scores derived from the simple footprint assessment board was correlated with these three criteria measured by CT, not only when the result of simple footprint assessment board was set as a non-continuous variable but also when the result was set as a continuous variable. The results of the age-stratified survey were similar for all groups.

Conclusions

The findings of this study suggest that a simple footprint assessment board can be potentially useful to detect flatfoot.

Trial registration

Retrospectively registered.
A cohort study of survival following discharge from hospital in rural Tanzanian children using linked data of admissions with community-based demographic surveillance
Authors: Mukasa Oscar , Masanja Honorati , DeSavigny Don , Schellenberg Joanna
Published: March 2021

Background

To illustrate the public health potential of linking individual bedside data with community-based household data in a poor rural setting, we estimated excess pediatric mortality risk after discharge from St Francis Designated District Hospital in Ifakara, Tanzania.

Methods

Linked data from demographic and clinical surveillance were used to describe post-discharge mortality and survival probability in children aged < 5 years, by age group and cause of admission. Cox regression models were developed to identify risk factors.

Results

Between March 2003 and March 2007, demographic surveillance included 28,910 children aged 0 to 5 years and among them 831 (3%) were admitted at least once to the district hospital. From all the children under the demographic surveillance 57,880 person years and 1381 deaths were observed in 24 months of follow up. Survivors of hospital discharge aged 0–5 years were almost two times more likely to die than children of the same age in the community who had not been admitted (RR = 1.9, P < 0.01, 95% CI 1.6, 2.4). Amongst children who had been admitted, mortality rate within a year was highest in infants (93 per 1000 person years) and amongst those admitted due to pneumonia and diarrhoea (97 and 85 per 1000 person years respectively). Those who lived 75 km or further from the district hospital, amongst children who were admitted and survived discharge from hospital, had a three times greater chance of dying within one year compared to those living within 25 km (adjusted HR 3.23, 95% CI 1.54,6.75). The probability of surviving the first 30 days post hospitalization was 94.4% [95% CI 94.4, 94.9], compared to 98.8% [95% CI 97.199.5] in non-hospitalized children of the same age in the commuity.

Conclusion

This study illustrates the potential of linking health related data from facility and household levels. Our results suggest that families may need additional support post hospitalization.
Research priorities for rare neurological diseases: a representative view of patient representatives and healthcare professionals from the European Reference Network for Rare Neurological Diseases
Authors: Post Annemarie E. M. , Klockgether Thomas , Landwehrmeyer G. Bernhard , Pandolfo Massimo , Arnesen Astri , Reinhard Carola , Graessner Holm
Published: March 2021

Background

Patient involvement in research increases the impact of research and the likelihood of adoption in clinical practice. A first step is to know which research themes are important for patients. We distributed a survey on research priorities to ERN-RND members, both patient representatives and healthcare professionals, asking them to prioritize five research themes for rare neurological diseases on a scale ranging from 1 (most important) to 5 (least important). A follow-up e-mail interview was conducted with patient representatives and professionals to assess potential reasons for differences in opinions between these two groups.

Results

In total, 156 responses were analysed: 61 from professionals and 95 from patient representatives. They covered all ERN-RND disease groups and came from 20 different EU countries. Almost half of the respondents considered ‘Developing therapies and preventive strategies’ the most important research theme. In particular, patient representatives prioritized this theme more often than professionals, while professionals prioritized ‘Disease mechanisms and models’.
Patient representatives indicated that therapies and prevention were of the utmost importance to them, because their lives are often heavily impacted by the disease and their main goal is to relief the burden of disease. Professionals indicated that investigating disease mechanisms will lead to more knowledge and is indispensable for finding new treatments.

Conclusions

Patients and professionals have different opinions on which research theme should have priority. A qualitative follow-up shows that they respect each others’ view points. Different stakeholders involved in research should be aware of their differences in research theme priority. Explaining these differences to each other leads to more understanding, and could improve patient engagement in research.

Graphical Abstract
EIF3F-related neurodevelopmental disorder: refining the phenotypic and expanding the molecular spectrum
Authors:   UCLA California Center for Rare Disease, Hüffmeier Ulrike , Kraus Cornelia , Reuter Miriam S. , Uebe Steffen , Abbott Mary-Alice , Ahmed Syed A. , Rawson Kristyn L. , Barr Eileen , Li Hong , Bruel Ange-Line , Faivre Laurence , Tran Mau-Them Frédéric , Botti Christina , Brooks Susan , Burns Kaitlyn , Ward D. Isum , Dutra-Clarke Marina , Martinez-Agosto Julian A. , Lee Hane , Nelson Stanley F. , Zacher Pia , Abou Jamra Rami , Klöckner Chiara , McGaughran Julie , Kohlhase Jürgen , Schuhmann Sarah , Moran Ellen , Pappas John , Raas-Rothschild Annick , Sacoto Maria J. Guillen , Henderson Lindsay B. , Palculict Timothy Blake , Mullegama Sureni V. , Zghal Elloumi Houda , Reich Adi , Schrier Vergano Samantha A. , Wahl Erica , Reis André , Zweier Christiane
Published: March 2021

Background

An identical homozygous missense variant in EIF3F, identified through a large-scale genome-wide sequencing approach, was reported as causative in nine individuals with a neurodevelopmental disorder, characterized by variable intellectual disability, epilepsy, behavioral problems and sensorineural hearing-loss. To refine the phenotypic and molecular spectrum of EIF3F-related neurodevelopmental disorder, we examined independent patients.

Results

21 patients were homozygous and one compound heterozygous for c.694T>G/p.(Phe232Val) in EIF3F. Haplotype analyses in 15 families suggested that c.694T>G/p.(Phe232Val) was a founder variant. All affected individuals had developmental delays including delayed speech development. About half of the affected individuals had behavioral problems, altered muscular tone, hearing loss, and short stature. Moreover, this study suggests that microcephaly, reduced sensitivity to pain, cleft lip/palate, gastrointestinal symptoms and ophthalmological symptoms are part of the phenotypic spectrum. Minor dysmorphic features were observed, although neither the individuals’ facial nor general appearance were obviously distinctive. Symptoms in the compound heterozygous individual with an additional truncating variant were at the severe end of the spectrum in regard to motor milestones, speech delay, organic problems and pre- and postnatal growth of body and head, suggesting some genotype–phenotype correlation.

Conclusions

Our study refines the phenotypic and expands the molecular spectrum of EIF3F-related syndromic neurodevelopmental disorder.
The reliability and validity of the Japanese version of the Daily Record of Severity of Problems (J-DRSP) and Development of a Short-Form version (J-DRSP (SF)) to assess symptoms of premenstrual syndrome among Japanese women
Authors: Ikeda Yumie , Egawa Miho , Okamoto Kazuya , Mandai Masaki , Takahashi Yoshimitsu , Nakayama Takeo
Published: March 2021

Purpose

To assess the validity and reliability of the Japanese version of the Daily Record of Severity of Problems (J-DRSP, 24 items) for evaluating symptoms of premenstrual syndrome (PMS), and to develop a short form version of the J-DRSP.

Methods

Using the “DRSP-JAPAN” smartphone app, we collected daily J-DRSP records from cycle day − 6 (CD − 6) to CD 10, with CD 1 representing the menstruation onset date. Factorial validity (exploratory factor analysis: EFA, confirmatory factor analysis: CFA) and criterion validity were examined, and test-retest reliability (intraclass correlation: ICC) evaluated. The short-form version of the J-DRSP was developed using classical test theory.

Results

In total, 304 women participated and 243 recorded symptoms on at least 4 days spanning the week of the luteal phase (CD − 6 to CD 0) and 4 days spanning the week of the follicular phase (CD 4 to CD 10), with CD 0 set as the day before menstruation started. The EFA revealed a two-factor structure. Kaiser-Meyer-Olkin was 0.992, and Bartlett’s test of sphericity chi-square was 3653.89 (P < 0.001). However, the model fitness of CFA was found to be suboptimal (comparative fit index (CFI): 0.83, root mean square error of approximation (RMSEA): 0.12). Total scores for J-DRSP and the sum scores for each subscale were higher on CD 0 than on CD 10 (p < 0.001), suggesting validity for some criteria. ICC values for the total J-DRSP score from CD 0 to CD − 1, and between CD 9 to CD 10, were 0.60 (95% CI: 0.48–0.72) and 0.76 (95% CI: 0.69–0.82), respectively. Having eliminated some original items after considering factor loading for each item, we developed an 8-item Short-Form J-DRSP (J-DRSP (SF)) comprising 2 factors (S-Psychological and S-Physical, 4 items for each). CFA showed a better model fit (CFI: 0.99, RMSEA: 0.048), and ICC values in the luteal and follicular phases were 0.61 (95%CI: 0.51–0.68) and 0.70 (95%CI: 0.62–0.77), respectively.

Conclusion

The J-DRSP has moderate to good reliability and a certain level of validity. The 8-item J-DRSP (SF) has a two-factor structure and can be used effectively among Japanese women to assess their PMS symptoms.
Development of a culturally sensitive Arabic version of the Mini International Neuropsychiatric Interview (M.I.N.I.-AR) and validation of the depression module
Authors: Karnouk Carine , Böge Kerem , Lindheimer Nico , Churbaji Dana , Abdelmagid Shaymaa , Mohamad Sara , Hahn Eric , Bajbouj Malek
Published: March 2021

Background

Arabic represents one of the most frequently spoken languages worldwide, especially among refugee populations. There is a pressing need for specialized diagnostic tools corresponding to the DSM-5 criteria in Modern Standard Arabic, which can be administered on Arabic speakers in the West and Arab region alike.

Objectives

To develop and validate the culturally-adapted version of the most recent M.I.N.I. 7.0.2 into Modern Standard Arabic—a form of Arabic commonly used across all Arab countries.

Methods

102 participants were recruited between April 2019 to March 2020 at the Charité - Universitätsmedizin in Berlin. Symptoms were assessed with Arabic versions of rater-based and self-rated measures, including Mini International Neuropsychiatric Interview (M.I.N.I.), Patient Health Questionnaire (PHQ-9), and Harvard Trauma Questionnaire (HTQ). Arabic-speaking psychiatrists saw participants for diagnostic assessment.

Results

Cohen’s kappa (κ) values were moderate for major depression, and slight for post-traumatic stress disorder, as well as generalized anxiety disorder. Moreover, kappa values indicated moderate agreement between M.I.N.I.-AR and PHQ-9 for depression, as well as HTQ for post-traumatic stress disorder, respectively.

Conclusion

The translated and culturally adapted version of the M.I.N.I. addresses an existing need for a reliable, efficient, and effective comprehensive diagnostic tool using the most recent DSM-5 criteria in Modern Standard Arabic (MSA). Based on the obtained results, only a validation of the depression module (Module A) of the M.I.N.I-AR was possible. Study outcomes also show evidence for the validation of Module H covering Post-Traumatic Stress Disorder. Potential valuable contributions can be extended to this translation and validation.
Third-line therapy for chronic myeloid leukemia: current status and future directions
Authors: Cortes Jorge , Lang Fabian
Published: March 2021

Chronic myeloid leukemia (CML) is driven by the BCR-ABL1 fusion protein, formed by a translocation between chromosomes 9 and 22 that creates the Philadelphia chromosome. The BCR-ABL1 fusion protein is an optimal target for tyrosine kinase inhibitors (TKIs) that aim for the adenosine triphosphate (ATP) binding site of ABL1. While these drugs have greatly improved the prognosis for CML, many patients ultimately fail treatment, some requiring multiple lines of TKI therapy. Mutations can occur in the ATP binding site of ABL1, causing resistance by preventing the binding of many of these drugs and leaving patients with limited treatment options. The approved TKIs are also associated with adverse effects that may lead to treatment discontinuation in some patients. Efficacy decreases with each progressive line of therapy; data suggest little clinical benefit of treatment with a third-line (3L), second-generation tyrosine kinase inhibitor (2GTKI) after failure of a first-generation TKI and a 2GTKI. Novel treatment options are needed for the patient population that requires treatment in the 3L setting and beyond. This review highlights the need for clear guidelines and new therapies for patients requiring 3L treatment and beyond.
Ovarian seromucinous tumors: clinicopathological features of 10 cases with a detailed review of the literature
Authors: Idrees Romana , Din Nasir Ud , Siddique Sabeehudin , Fatima Saira , Abdul-Ghafar Jamshid , Ahmad Zubair
Published: March 2021

Background

The 2014 WHO Classification of ovarian neoplasms introduced a new entity of seromucinous tumors associated with endometriosis. These tumors encompassed a spectrum from benign to malignant and included seromucinous cystadenoma/ cystadenofibroma, seromucinous borderline tumor/atypical proliferative seromucinous tumor and seromucinous carcinoma. However, the 2020 WHO Classification of Female Genital Tumours removed seromucinous carcinomas as a distinct entity and recategorized them as Endometrioid carcinomas with mucinous differentiation. Here we describe clinico-morphologic features of seromucinous tumors recategorizing cases originally diagnosed as seromucinous carcinoma in light of 2020 WHO classification and present detailed review of literature.

Methods

Slides of seromucinous tumors were reviewed. Special emphasis was given to evaluation of stromal invasion. Follow-up was obtained.

Results

Ten cases were diagnosed. Mean age was 40 years. Four cases were bilateral. Mean size was 19 cm. Grossly; luminal papillary projections were seen in 6 cases. Tumors demonstrated a papillary architecture with papillae lined by stratified seromucinous epithelium showing nuclear atypia. Stromal invasion was seen in 4 cases. Six cases were reported as borderline seromucinous tumors and 4 cases originally diagnosed as seromucinous carcinoma were recategorized as endometrioid carcinoma with mucinous differentiation on review. Endometriosis was seen in 4 cases. CK7, PAX8 and ER were positive in 7/7 cases. Two cases showed extra-ovarian involvement. Follow up was available in 7 cases. Six patients were alive and well at follow up ranging from 8 to 46 months. Six patients received chemotherapy postoperatively. One patient with carcinoma died of disease 18 months postoperatively.

Conclusion

In our series, 4 cases were originally diagnosed as seromucinous carcinomas. However, these were recategorized in light of the 2020 WHO Classification of Female Genital tumors as endometrioid carcinomas with mucinous differentiation. Six cases were diagnosed as seromucinous borderline tumors. Thus, majority of cases were borderline in agreement with published literature.
Molecular survey of vector-borne diseases in two groups of domestic dogs from Lisbon, Portugal
Authors: Dordio Ana Mafalda , Beck Relja , Nunes Telmo , Pereira da Fonseca Isabel , Gomes Jacinto
Published: March 2021

Background

Canine vector-borne diseases (CVBDs) are caused by a wide range of pathogens transmitted by arthropods. They have been an issue of growing importance in recent years; however, there is limited information about the vector-borne pathogens circulating in Portugal. The aim of the present study was to detect canine vector-borne bacteria and protozoa of veterinary and zoonotic importance using molecular methods.

Methods

One hundred and forty-two dogs from Lisbon, southern Portugal, were tested: 48 dogs from a veterinary hospital clinically suspected of vector-borne diseases and 94 apparently healthy dogs from shelters. Anaplasma spp./Ehrlichia spp., Babesia/Theileria spp., Hepatozoon spp., and Mycoplasma spp. infections were detected by PCR from blood samples and examined under light microscopy. Other information including clinical status and diagnostic test results were collected for each animal.

Results

Infections were detected by PCR in 48 (33.80%) dogs. Single infections were found in 35 dogs (24.64%), and co-infections were found in 13 (9.15%) dogs. Twenty-nine (20.42%) dogs were positive for Hepatozoon spp., 15 (10.56%) for Mycoplasma spp., 11 (7.75%) for Anaplasma spp./Ehrlichia spp., and six (4.21%) for Babesia spp. DNA sequencing was used to identify Babesia vogeli (2.81%), Babesia canis (1.40%), Hepatozoon canis (20.42%), Mycoplasma haematoparvum (2.11%), Mycoplasma haemocanis (8.45%), Anaplasma platys (7.04%), and Ehrlichia canis (0.70%).

Conclusions

This is the first molecular identification of B. canis and M. haematoparvum in dogs from southern Portugal. This study highlights the importance of molecular methods to identify CVBD pathogens in endemic areas and helps to guide the clinical approach of veterinarians in practice.

Graphical Abstract
Diet-induced obesity in animal models: points to consider and influence on metabolic markers
Authors: de Moura e Dias Mariana , dos Reis Sandra Aparecida , da Conceição Lisiane Lopes , Sediyama Catarina Maria Nogueira de Oliveira , Pereira Solange Silveira , de Oliveira Leandro Licursi , Gouveia Peluzio Maria do Carmo , Martinez J. Alfredo , Milagro Fermín Ignacio
Published: March 2021

Overweight and obesity are a worldwide public health problem. Obesity prevalence has increased considerably, which indicates the need for more studies to better understand these diseases and related complications. Diet induced-obesity (DIO) animal models can reproduce human overweight and obesity, and there are many protocols used to lead to excess fat deposition. So, the purpose of this review was to identify the key points for the induction of obesity through diet, as well as identifying which are the necessary endpoints to be achieved when inducing fat gain. For this, we reviewed the literature in the last 6 years, looking for original articles that aimed to induce obesity through the diet. All articles evaluated should have a control group, in order to verify the results found, and had worked with Sprague–Dawley and Wistar rats, or with C57BL-/-6 mice strain. Articles that induced obesity by other methods, such as genetic manipulation, surgery, or drugs were excluded, since our main objective was to identify key points for the induction of obesity through diet. Articles in humans, in cell culture, in non-rodent animals, as well as review articles, articles that did not have obesity induction and book chapters were also excluded. Body weight and fat gain, as well as determinants related to inflammation, hormonal concentration, blood glycemia, lipid profile, and liver health, must be evaluated together to better determination of the development of obesity. In addition, to select the best model in each circumstance, it should be considered that each breed and sex respond differently to diet-induced obesity. The composition of the diet and calorie overconsumption are also relevant to the development of obesity. Finally, it is important that a non-obese control group is included in the experimental design.
Practical challenges in oral immunotherapy resolved through patient-centered care
Authors: Graham François , Mack Douglas P. , Bégin Philippe
Published: March 2021

Oral immunotherapy (OIT) is now widely recognized as a valid option for the management of IgE-mediated food allergies. However, in real-life practice, OIT can lead to a variety of unique situations where the best course of action is undetermined. In patient-centered care, individual patient preferences, needs and values, should guide all clinical decisions. This can be achieved by using shared-decision making and treatment customization to navigate areas of uncertainty in a way that is responsive to patient’s needs and preferences. However, in the context of OIT, lack of awareness of potential protocol adaptability or alternatives can become a barrier to treatment personalization. The purpose of this article is to review the theoretical bases of patient-centered care and shared decision-making and their practical implication for the patient-centered delivery of OIT. Clinical cases highlighting common challenges in real-life OIT practice are presented along with a discussion of potential personalized management options to be considered. While the practice of OIT is bound to evolve as additional scientific and experiential knowledge is gained, it should always remain rooted in the general principles of patient-centered care.
A profile and review of findings from the Early Markers for Autism study: unique contributions from a population-based case–control study in California
Authors: Lyall Kristen , Ames Jennifer L. , Pearl Michelle , Traglia Michela , Weiss Lauren A. , Windham Gayle C. , Kharrazi Martin , Yoshida Cathleen K. , Yolken Robert , Volk Heather E. , Ashwood Paul , Van de Water Judy , Croen Lisa A.
Published: March 2021

Background

The Early Markers for Autism (EMA) study is a population-based case–control study designed to learn more about early biologic processes involved in ASD.

Methods

Participants were drawn from Southern California births from 2000 to 2003 with archived prenatal and neonatal screening specimens. Across two phases, children with ASD (n = 629) and intellectual disability without ASD (ID, n = 230) were ascertained from the California Department of Developmental Services (DDS), with diagnoses confirmed according to DSM-IV-TR criteria based on expert clinical review of abstracted records. General population controls (GP, n = 599) were randomly sampled from birth certificate files and matched to ASD cases by sex, birth month and year after excluding individuals with DDS records. EMA has published over 20 papers examining immune markers, endogenous hormones, environmental chemicals, and genetic factors in association with ASD and ID. This review summarizes the results across these studies, as well as the EMA study design and future directions.

Results

EMA enabled several key contributions to the literature, including the examination of biomarker levels in biospecimens prospectively collected during critical windows of neurodevelopment. Key findings from EMA include demonstration of elevated cytokine and chemokine levels in maternal mid-pregnancy serum samples in association with ASD, as well as aberrations in other immune marker levels; suggestions of increased odds of ASD with prenatal exposure to certain endocrine disrupting chemicals, though not in mixture analyses; and demonstration of maternal and fetal genetic influence on prenatal chemical, and maternal and neonatal immune marker and vitamin D levels. We also observed an overall lack of association with ASD and measured maternal and neonatal vitamin D, mercury, and brain-derived neurotrophic factor (BDNF) levels.

Limitations

Covariate and outcome data were limited to information in Vital Statistics and DDS records. As a study based in Southern California, generalizability for certain environmental exposures may be reduced.

Conclusions

Results across EMA studies support the importance of the prenatal and neonatal periods in ASD etiology, and provide evidence for the role of the maternal immune response during pregnancy. Future directions for EMA, and the field of ASD in general, include interrogation of mechanistic pathways and examination of combined effects of exposures.
Signet ring cell carcinoma of rectum metastasizing to synchronous renal cell carcinoma: a case report
Authors: Krsteska Blagica , Jovanovic Rubens , Eftimov Aleksandar , Ilievski Boro , Hadzi-Mancev Dragan , Osmani Bujar , Kostadinova-Kunovska Slavica
Published: March 2021

Background

Rectal signet ring cell carcinoma is a rare type of colorectal adenocarcinoma characterized by an aggressive biological behavior and poor prognosis. The co-occurrence of colorectal carcinoma and renal cell carcinoma (RCC) has found in many hundreds of patients, many of whom also have additional malignancies. Cancer to cancer metastasis is rare and an uncommon phenomenon in malignancy, especially at the time of initial diagnosis, suggesting a genetic susceptibility.

Case presentation

We present the case of a 66-year-old Macedonian man with synchronous rectal signet ring cell carcinoma and RCC with tumor to tumor metastasis feature. He underwent a left nephrectomy and anterior rectal resection after complaining of constipation for 3–4 months and the appearance of synchronous tumors on the imaging studies. Morphology and immunohistochemical analysis of specimens from the RCC revealed signet ring cells identical to the rectal signet ring cell carcinoma. The next-generation sequencing study revealed mutations in TP53 and ERBB2, and microsatellite stable signet ring cell carcinoma was determined by deoxyribonucleic acid (DNA) sequencing.

Conclusions

Cancer to cancer metastasis, although rare, needs to be considered in synchronous tumors. RCC, when diagnosed in multiple synchronous tumors, should be examined carefully. The paucity of reported cases indicates the need for advanced research in imaging methods for metastasis and new therapeutic approaches.
Alterations of mesenchymal stromal cells in cerebrospinal fluid: insights from transcriptomics and an ALS clinical trial
Authors: Krull Ashley A. , Setter Deborah O. , Gendron Tania F. , Hrstka Sybil C. L. , Polzin Michael J. , Hart Joseph , Dudakovic Amel , Madigan Nicolas N. , Dietz Allan B. , Windebank Anthony J. , van Wijnen Andre J. , Staff Nathan P.
Published: March 2021

Background

Mesenchymal stromal cells (MSCs) have been studied with increasing intensity as clinicians and researchers strive to understand the ability of MSCs to modulate disease progression and promote tissue regeneration. As MSCs are used for diverse applications, it is important to appreciate how specific physiological environments may stimulate changes that alter the phenotype of the cells. One need for neuroregenerative applications is to characterize the spectrum of MSC responses to the cerebrospinal fluid (CSF) environment after their injection into the intrathecal space. Mechanistic understanding of cellular biology in response to the CSF environment may predict the ability of MSCs to promote injury repair or provide neuroprotection in neurodegenerative diseases.

Methods

In this study, we characterized changes in morphology, metabolism, and gene expression occurring in human adipose-derived MSCs cultured in human (hCSF) or artificial CSF (aCSF) as well as examined relevant protein levels in the CSF of subjects treated with MSCs for amyotrophic lateral sclerosis (ALS).

Results

Our results demonstrated that, under intrathecal-like conditions, MSCs retained their morphology, though they became quiescent. Large-scale transcriptomic analysis of MSCs revealed a distinct gene expression profile for cells cultured in aCSF. The aCSF culture environment induced expression of genes related to angiogenesis and immunomodulation. In addition, MSCs in aCSF expressed genes encoding nutritional growth factors to expression levels at or above those of control cells. Furthermore, we observed a dose-dependent increase in growth factors and immunomodulatory cytokines in CSF from subjects with ALS treated intrathecally with autologous MSCs.

Conclusions

Overall, our results suggest that MSCs injected into the intrathecal space in ongoing clinical trials remain viable and may provide a therapeutic benefit to patients.
Online marketing practices of regenerative medicine clinics in US-Mexico border region: a web surveillance study
Authors: Chavez Javier , Shah Neal A. , Ruoss Severin , Cuomo Raphael E. , Ward Samuel R. , Mackey Tim K.
Published: March 2021

Introduction

The potential of regenerative medicine to improve human health has led to the rapid expansion of stem cell clinics throughout the world with varying levels of regulation and oversight. This has led to a market ripe for stem cell tourism, with Tijuana, Mexico, as a major destination. In this study, we characterize the online marketing, intervention details, pricing of services, and assess potential safety risks through web surveillance of regenerative medicine clinics marketing services in Tijuana.

Methods

We conducted structured online search queries from March to April 2019 using 296 search terms in English and Spanish on two search engines (Google and Bing) to identify websites engaged in direct-to-consumer advertising of regenerative medicine services. We performed content analysis to characterize three categories of interest: online presence, tokens of scientific legitimacy, and intervention details.

Results

Our structured online searches resulted in 110 unique websites located in Tijuana corresponding to 76 confirmed locations. These clinics’ online presence consisted of direct-to-consumer advertising mainly through a dedicated website (94.5%) or Facebook page (65.5%). The vast majority of these websites (99.1%) did not mention any affiliation to an academic institutions or other overt tokens of scientific legitimacy. Most clinics claimed autologous tissue was the source of treatments (67.3%) and generally did not specify route of administration. Additionally, of the Tijuana clinics identified, 13 claimed licensing, though only 1 matched with available licensing information.

Conclusions

Regenerative medicine clinics in Tijuana have a significant online presence using direct-to-consumer advertising to attract stem-cell tourism clientele in a bustling border region between Mexico and the USA. This study adds to existing literature evidencing the unregulated nature of online stem cell offerings and provides further evidence of the need for regulatory harmonization, particularly to address stem cell services being offered online across borders.