bluuebunny/crossref_metadata_2025 huggingface dataset:
Benign but Terminal: Cardiopulmonary Collapse from a Massive Chest Wall Lipoma
Authors: Paulraj Shweta , Harne Prateek Suresh , Mirchia Kanish , Mian Sundus , Sohal Raman , Habib Gaston , Shah Amish , Amzuta Ioana
Published: August 2020

Lipomas are the most common benign soft tissue tumor. Yet, strikingly simple tumors can become problematic when compounded by odd characteristics such as size and location. We report the case of a 53-year-old male who developed complete right lung collapse secondary to a large right-sided chest wall lipoma with accelerated growth in the past 6 months. Bronchoscopy revealed extrinsic compression of the right mainstem bronchus. Histopathology of the soft tissue mass was suggestive of a lipoma. The mass was not amenable to surgery due to a high risk of mortality from his underlying comorbidities. His hospital stay was complicated by progressive end-stage restrictive lung disease necessitating intubation and eventually a tracheostomy, recurrent pneumonias, multiorgan dysfunction, and his eventual demise. We highlight a rare presentation of an unchecked lipoma, which ultimately led to the death of our patient. Simple lipomas show insidious growth and can remain asymptomatic until they reach a large size. Chest wall tumors should be considered malignant until proven otherwise by excisional biopsy. This reiterates the need to treat all chest wall tumors with wide resection in order to provide the best chance for cure.
Perceiving and Addressing the Pervasive Racial Disparity in Abortion
Authors: Studnicki James , Fisher John W. , Sherley James L.
Published: August 2020

Black women have been experiencing induced abortions at a rate nearly 4 times that of White women for at least 3 decades, and likely much longer. The impact in years of potential life lost, given abortion’s high incidence and racially skewed distribution, indicates that it is the most demographically consequential occurrence for the minority population. The science community has refused to engage on the subject and the popular media has essentially ignored it. In the current unfolding environment, there may be no better metric for the value of Black lives.
Malaysia’s Posture in the Indo-Pacific Construct
Authors: Krishnan Tharishini
Published: August 2020

The Indo-Pacific (IP), the region covering the Indian Ocean and the Pacific Region, is concurrently shaping the posture of international affairs. As a littoral state and critical partner in the IP construct, Malaysia’s responses to this stance are inevitable due to its geostrategic location in the construct. This article argues that Malaysia’s posture vis-à-vis the IP as that of a ‘neutralist’. The discussion is divided into two sections. The first section describes weaknesses in the quadrilateral security dialogues (Quad) centrality using the features of regional security complex theory (RSCT). The second section discusses Malaysia’s neutrality vis-à-vis the IP construct. The article argues that, while opportunities can be seen in terms of strengthening the existing relations and tapping into new areas of partnership, Malaysia may face challenges in the form of marginalisation and entrapment. Apprehension is still prominent; therefore, the concept is in a ‘wait and see’ mode. The article concludes that the catalyst is found by drawing a more effective vision of the concept and is the key, particularly if the IP aspires to attract and appeal to Southeast Asian countries such as Malaysia.
Prevalence and Type of Sexual Dysfunction in Female Patients Receiving Antidepressant Medications
Authors: Grover Sandeep , Kate Natasha , Mishra Eepsita , Avasthi Ajit
Published: August 2020

Aim: To assess the prevalence and typology of sexual dysfunction in female patients receiving antidepressant medications using the Arizona Sexual Experience Scale (ASEX).

Method: A cross-sectional design was employed. A total of 71 married women with various psychiatric disorders receiving antidepressants for at least 3 months’ were evaluated on ASEX, Brief Adherence Rating Scale, Medication Adherence Questionnaire, and Global Assessment of Functioning (GAF) scale. Subjects with a history of sexual dysfunction prior to psychotropic intake, menopause, severe interpersonal relationship problems with spouse, or chronic medical illness were excluded.

Results: The study sample had the mean age of 37.35 (SD: 6.82) years. More than four-fifth (80.2%) of patients had sexual dysfunction as per the ASEX. Using a cutoff score of 4 or more to define sexual dysfunction in various domains, decreased desire was seen in 81.7%, reduced arousal was seen in 80.3%, poor vaginal lubrication was seen in 76.1%, reduced satisfaction was seen in 57.7%, and reduced ability to reach orgasm was seen in 50.7%. Despite this, few patients (13.3%) discussed their sexual dysfunction with their treating psychiatrist. Sexual dysfunction did not influence the medication adherence.

Conclusions: Sexual dysfunction is quite prevalent in female patients receiving antidepressant medications; however, this is not adequately discussed by the patient or the treating psychiatrist.
Impact of gemtuzumab ozogamicin on MRD and relapse risk in patients with NPM1-mutated AML: results from the AMLSG 09-09 trial
Authors: Kapp-Schwoerer Silke , Weber Daniela , Corbacioglu Andrea , Gaidzik Verena I. , Paschka Peter , Krönke Jan , Theis Frauke , Rücker Frank G. , Teleanu Maria-Veronica , Panina Ekaterina , Jahn Nikolaus , Herzig Julia , Kubanek Lena , Schrade Anika , Göhring Gudrun , Fiedler Walter , Kindler Thomas , Schroeder Thomas , Mayer Karin T. , Lübbert Michael , Wattad Mohammed , Götze Katharina S. , Horst Heinz A. , Koller Elisabeth , Wulf Gerald , Schleicher Jan , Bentz Martin , Krauter Jürgen , Bullinger Lars , Krzykalla Julia , Benner Axel , Schlenk Richard F. , Thol Felicitas , Heuser Michael , Ganser Arnold , Döhner Hartmut , Döhner Konstanze
Published: August 2020

Monitoring of measurable residual disease (MRD) provides prognostic information in patients with Nucleophosmin1-mutated (NPM1mut) acute myeloid leukemia (AML) and represents a powerful tool to evaluate treatment effects within clinical trials. We determined NPM1mut transcript levels (TLs) by quantitative reverse-transcription polymerase chain reaction and evaluated the prognostic impact of NPM1mut MRD and the effect of gemtuzumab ozogamicin (GO) on NPM1mut TLs and the cumulative incidence of relapse (CIR) in patients with NPM1mut AML enrolled in the randomized phase 3 AMLSG 09-09 trial. A total of 3733 bone marrow (BM) samples and 3793 peripheral blood (PB) samples from 469 patients were analyzed. NPM1mut TL log10 reduction ≥ 3 and achievement of MRD negativity in BM and PB were significantly associated with a lower CIR rate, after 2 treatment cycles and at end of treatment (EOT). In multivariate analyses, MRD positivity was consistently revealed to be a poor prognostic factor in BM and PB. With regard to treatment effect, the median NPM1mut TLs were significantly lower in the GO-Arm across all treatment cycles, resulting in a significantly greater proportion of patients achieving MRD negativity at EOT (56% vs 41%; P = .01). The better reduction in NPM1mut TLs after 2 treatment cycles in MRD positive patients by the addition of GO led to a significantly lower CIR rate (4-year CIR, 29.3% vs 45.7%, P = .009). In conclusion, the addition of GO to intensive chemotherapy in NPM1mut AML resulted in a significantly better reduction in NPM1mut TLs across all treatment cycles, leading to a significantly lower relapse rate.
Neutrophils from hereditary hemochromatosis patients are protected from iron excess and are primed
Authors: Renassia Cyril , Louis Sabine , Cuvellier Sylvain , Boussetta Nadia , Deschemin Jean-Christophe , Borderie Didier , Bailly Karine , Poupon Joel , Dang Pham My-Chan , El-Benna Jamel , Manceau Sandra , Lefrère François , Vaulont Sophie , Peyssonnaux Carole
Published: August 2020

Iron is required for the oxidative response of neutrophils to allow the production of reactive oxygen species (ROS). However, neutrophil function may be severely altered in conditions of iron overload, as observed in chronically transfused patients. Therefore, a tight regulation of neutrophil iron homeostasis seems to be critical for avoiding iron toxicity. Hepcidin is the key iron regulator in organisms; however, no studies have investigated its role in maintaining neutrophil iron homeostasis or characterized neutrophil function in patients with hereditary hemochromatosis (HH), a common iron overload genetic disorder that results from a defect in hepcidin production. To explore these issues, we studied 2 mouse models of iron overload: an experimentally induced iron overload model (EIO), in which hepcidin is increased, and a genetic HH model of iron overload with a deletion of hepatic hepcidin. We found that iron-dependent increase of hepatic hepcidin results in neutrophil intracellular iron trapping and consecutive defects in oxidative burst activity. In contrast, in both HH mouse models and HH patients, the lack of hepcidin expression protects neutrophils from toxic iron accumulation. Moreover, systemic iron overload correlated with a surprising neutrophil priming and resulted in a more powerful oxidative burst. Indeed, important factors in neutrophil priming and activation, such as tumor necrosis factor α (TNF-α), VCAM-1, and ICAM-1 are increased in the plasma of HH patients and are associated with an increase in HH neutrophil phagocytosis capacity and a decrease in L-selectin surface expression. This is the first study to characterize neutrophil iron homeostasis and associated functions in patients with HH.
Biological and structural characterization of murine TRALI antibody reveals increased Fc-mediated complement activation
Authors: Zeeuw van der Laan Eveline A. N. , van der Velden Saskia , Bentlage Arthur E. H. , Larsen Mads D. , van Osch Thijs L. J. , Mok Juk Yee , Brasser Giso , Geerdes Dionne M. , Koeleman Carolien A. M. , Nouta Jan , Semple John W. , Porcelijn Leendert , van Esch Wim J. E. , Wuhrer Manfred , van der Schoot C. Ellen , Vidarsson Gestur , Kapur Rick
Published: August 2020

Transfusion-related acute lung injury (TRALI) remains a leading cause of transfusion-related deaths. In most cases, anti-leukocyte antibodies in the transfusion product trigger TRALI, but not all anti-leukocyte antibodies cause TRALI. It has been shown that the anti–major histocompatibility complex (MHC) class I antibody 34-1-2S (anti–H-2Kd) causes TRALI in BALB/c mice (MHC class I haplotype H-2Kd), whereas SF1.1.10 (anti–H-2Kd) does not. In C57BL/6 mice (MHC class I haplotype H-2Kb), TRALI only occurs when anti-MHC class I antibody AF6-88.5.5.3 (anti–H-2Kb) is administered together with a high dose of 34-1-2S. It remains unknown which specific antibody characteristics are responsible for eliciting TRALI. We therefore investigated several biological and structural features of 34-1-2S compared with other anti-MHC class I antibodies, which on their own do not cause TRALI: SF1.1.10 and AF6-88.5.5.3. No substantial differences were observed between the TRALI-causing 34-1-2S and the TRALI-resistant SF1.1.10 regarding binding affinity to H-2Kd. Regarding binding affinity to H-2Kb, only AF6-88.5.5.3 potently bound to H-2Kb, whereas 34-1-2S exhibited weak but significant cross-reactivity. Furthermore, the binding affinity to FcγRs as well as the Fc glycan composition seemed to be similar for all antibodies. Similar Fc glycosylation profiles were also observed for human TRALI-causing donor anti-HLA antibodies compared with human anti-HLA antibodies from control donors. 34-1-2S, however, displayed superior complement activation capacity, which was fully Fc dependent and not significantly dependent on Fc glycosylation. We conclude that TRALI induction is not correlated with Fab- and Fc-binding affinities for antigen and FcγRs, respectively, nor with the composition of Fc glycans; but increased Fc-mediated complement activation is correlated with TRALI induction.
Lymphangioleiomyomatosis: a clinical review
Authors: O'Mahony Anne M. , Lynn Evelyn , Murphy David J. , Fabre Aurelie , McCarthy Cormac
Published: August 2020

Lymphangioleiomyomatosis (LAM) is a diffuse cystic lung disease. There are two main types of LAM: sporadic, and LAM associated with the tuberous sclerosis complex (TSC), which is caused by mutations in theTSC1andTSC2genes. LAM is characterised by cystic lung disease resulting in progressive dyspnoea, renal angiomyolipomas and lymphatic complications. Pneumothorax occurs frequently (70%) and definitive management with pleurodesis is recommended as the risk of recurrence is high. Characteristic thin-walled cysts are seen on computed tomography and the presence of elevated serum levels of a vascular endothelial growth factor-D has good diagnostic specificity. Currently, no single clinical or serological factor has been shown to predict prognosis. However, over the past decade, significant advances in our understanding of the pathophysiology of LAM has led to improved recognition of this rare disease and identification of treatment options. Mechanistic target of rapamycin inhibitors slow the rate of lung function decline and can resolve chylous effusion and regress angiomyolipomas. Life expectancy in patients with LAM is favourable, with a mean transplant-free survival >20 years from the time of diagnosis. Continued advances in understanding the molecular basis of LAM will lead to improved therapeutic targets and the development of more robust prognostic indicators.

Educational aims

To illustrate the clinical features, common presentations and radiological features of LAM

To outline the diagnostic approach to LAM, including the role of VEGF-D

To review the current prognostic indicators in LAM, and outline the impact of lung function, hormonal status, VEGF-D and clinical presentation on outcome

To inform clinicians on the management options for LAM both pharmacological and nonpharmacological
Sigmoid vaginoplasty in Mayer-Rokitansky-Kuster-Hauser syndrome
Authors: Amadou Magagi Ibrahim , Adamou Harissou , Oumarou Garba Souleymane , Halidou Maazou , Adakal Ousseini , Habou Oumarou , Abdoulaye Maman Bachir , Nayama Madi , Sani Rachid
Published: August 2020

Introduction

Mayer-Rokitansky-Kuster-Hauser syndrome (MRKH) is characterized by congenital aplasia of the uterus and upper 2/3 of the vagina, with normal female secondary sexual characteristics and a normal karyotype (46, XX). The frequency is 1/4500–5000 female births. The aim of this study was to report the management of MRKH syndrome with sigmoid vaginoplasty.

Patients and method

This study included 4 patients recruited over a 4-year period from February 2016 to January 2019. MRKH syndrome was retained in the presence of normal secondary sexual characteristics with normal external genitalia associated with vaginal aplasia and uterine agenesis. The approach was a laparotomy and a perineal approach under general anesthesia. The procedure involved the removal of a sigmoidal colonic graft that was anastomosed with the vaginal dimple.

Results

The average age was 23 years. All patients had consulted for primary amenorrhea, infertility, and/or difficulties in sexual intercourse. The diagnosis of MRKH type 1 was retained in all patients. The average length of the vagina was 3.25 cm before surgery and 13.63 cm after surgery. The postoperative outcomes were uneventful in 3 patients. One patient developed anastomotic stenosis that was successfully treated with vaginal dilation for 2 weeks. The average postoperative follow-up was 30 months.

Conclusion

In the context of a low-resource setting, sigmoid transposition represents a good procedure to treat vaginal aplasia and restore a satisfactory sexual activity to patients with MRKH type 1.
Elucidating the fate of nanoparticles among key cell components of the tumor microenvironment for promoting cancer nanotechnology
Authors: Bromma Kyle , Bannister Aaron , Kowalewski Antonia , Cicon Leah , Chithrani Devika B.
Published: August 2020

Successful integration of nanotechnology into the current paradigm of cancer therapy requires proper understanding of the interface between nanoparticles (NPs) and cancer cells, as well as other key components within the tumor microenvironment (TME), such as normal fibroblasts (FBs) and cancer-associated FBs (CAFs). So far, much focus has been on cancer cells, but FBs and CAFs also play a critical role: FBs suppress the tumor growth while CAFs promote it. It is not yet known how NPs interact with FBs and CAFs compared to cancer cells. Hence, our goal was to elucidate the extent of NP uptake, retention, and toxicity in cancer cells, FBs, and CAFs to further understand the fate of NPs in a real tumor-like environment. The outcome of this would guide designing of NP-based delivery systems to fully exploit the TME for a better therapeutic outcome. We used gold nanoparticles as our model NP system due to their numerous applications in cancer therapy, including radiotherapy and chemotherapy. A cervical cancer cell line, HeLa, and a triple-negative breast cancer cell line, MDA-MB-231 were chosen as cancer cell lines. For this study, a clinically feasible 0.2 nM concentration of GNPs was employed. According to our results, the cancer cells and CAFs had over 25- and 10-fold higher NP uptake per unit cell volume compared to FBs, respectively. Further, the cancer cells and CAFs had over 30% higher NP retention compared to FBs. There was no observed significant toxicity due to GNPs in all the cell lines studied. Higher uptake and retention of NPs in cancer cells and CAFs vs FBs is very important in promoting NP-based applications in cancer therapy. Our results show potential in modulating uptake and retention of GNPs among key components of TME, in an effort to develop NP-based strategies to suppress the tumor growth. An ideal NP-based platform would eradicate tumor cells, protect FBs, and deactivate CAFs. Therefore, this study lays a road map to exploit the TME for the advancement of “smart” nanomedicines that would constitute the next generation of cancer therapeutics.
Prediction of genomic breeding values based on pre-selected SNPs using ssGBLUP, WssGBLUP and BayesB for Edwardsiellosis resistance in Japanese flounder
Authors: Lu Sheng , Liu Yang , Yu Xijiang , Li Yangzhen , Yang Yingming , Wei Min , Zhou Qian , Wang Jie , Zhang Yingping , Zheng Weiwei , Chen Songlin
Published: August 2020

Background

Edwardsiella tarda causes acute symptoms with ascites in Japanese flounder (Paralichthys olivaceus) and is a major problem for China’s aquaculture sector. Genomic selection (GS) has been widely adopted in breeding industries because it shortens generation intervals and results in the selection of individuals that have great breeding potential with high accuracy. Based on an artificial challenge test and re-sequenced data of 1099 flounders, the aims of this study were to estimate the genetic parameters of resistance to E. tarda in Japanese flounder and to evaluate the accuracy of single-step GBLUP (ssGBLUP), weighted ssGBLUP (WssGBLUP), and BayesB for improving resistance to E. tarda by using three subsets of pre-selected single nucleotide polymorphisms (SNPs). In addition, SNPs that are associated with this trait were identified using a single-SNP genome-wide association study (GWAS) and WssGBLUP.

Results

We estimated a heritability of 0.13 ± 0.02 for resistance to E. tarda in Japanese flounder. One million SNPs at fixed intervals were selected from 4,978,724 SNPs that passed quality controls. GWAS identified significant SNPs on chromosomes 14 and 24. WssGBLUP revealed that the putative quantitative trait loci on chromosomes 1 and 14 contained SNPs that explained more than 1% of the genetic variance. Three 50 k-SNP subsets were pre-selected based on different criteria. Compared with pedigree-based prediction (ABLUP), the three genomic methods evaluated resulted in at least 7.7% greater accuracy of predictions. The accuracy of these genomic prediction methods was almost unchanged when pre-selected trait-related SNPs were used for prediction.

Conclusions

Resistance to E. tarda in Japanese flounder has a low heritability. GWAS and WssGBLUP revealed that the genetic architecture of this trait is polygenic. Genomic prediction of breeding values performed better than ABLUP. It is feasible to implement genomic selection to increase resistance to E. tarda in Japanese flounder with 50 k SNPs. Based on the criteria used here, pre-selection of SNPs was not beneficial and other criteria for pre-selection should be considered.
Rapid size change associated with intra-island evolutionary radiation in extinct Caribbean “island-shrews”
Authors: Woods Roseina , Turvey Samuel T. , Brace Selina , McCabe Christopher V. , Dalén Love , Rayfield Emily J. , Brown Mark J. F. , Barnes Ian
Published: August 2020

Background

The Caribbean offers a unique opportunity to study evolutionary dynamics in insular mammals. However, the recent extinction of most Caribbean non-volant mammals has obstructed evolutionary studies, and poor DNA preservation associated with tropical environments means that very few ancient DNA sequences are available for extinct vertebrates known from the region’s Holocene subfossil record. The endemic Caribbean eulipotyphlan family Nesophontidae (“island-shrews”) became extinct ~ 500 years ago, and the taxonomic validity of manyNesophontesspecies and their wider evolutionary dynamics remain unclear. Here we use both morphometric and palaeogenomic methods to clarify the status and evolutionary history ofNesophontesspecies from Hispaniola, the second-largest Caribbean island.

Results

Principal component analysis of 65Nesophontesmandibles from late Quaternary fossil sites across Hispaniola identified three non-overlapping morphometric clusters, providing statistical support for the existence of three size-differentiated HispaniolanNesophontesspecies. We were also able to extract and sequence ancient DNA from a ~ 750-year-old specimen ofNesophontes zamicrus, the smallest non-volant Caribbean mammal, including a whole-mitochondrial genome and partial nuclear genes.Nesophontes paramicrus(39-47 g) andN. zamicrus(~ 10 g) diverged recently during the Middle Pleistocene (mean estimated divergence = 0.699 Ma), comparable to the youngest species splits in Eulipotyphla and other mammal groups. Pairwise genetic distance values forN. paramicrusandN. zamicrusbased on mitochondrial and nuclear genes are low, but fall within the range of comparative pairwise data for extant eulipotyphlan species-pairs.

Conclusions

Our combined morphometric and palaeogenomic analyses provide evidence for multiple co-occurring species and rapid body size evolution in HispaniolanNesophontes, in contrast to patterns of genetic and morphometric differentiation seen in Hispaniola’s extant non-volant land mammals. Different components of Hispaniola’s mammal fauna have therefore exhibited drastically different rates of morphological evolution. Morphological evolution inNesophontesis also rapid compared to patterns across the Eulipotyphla, and our study provides an important new example of rapid body size change in a small-bodied insular vertebrate lineage. The Caribbean was a hotspot for evolutionary diversification as well as preserving ancient biodiversity, and studying the surviving representatives of its mammal fauna is insufficient to reveal the evolutionary patterns and processes that generated regional diversity.
Comprehensive geriatric assessment in older patients with cancer: an external validation of the multidimensional prognostic index in a French prospective cohort study
Authors: Liuu Evelyne , Hu Chunyun , Valero Simon , Brunet Thomas , Jamet Amelie , Bureau Marie-Laure , Pilotto Alberto , Saulnier Pierre-Jean , Paccalin Marc
Published: August 2020

Background

Older patients with cancer require specific and individualized management. The 3-group Multidimensional Prognostic Index (MPI) based on the Comprehensive Geriatric Assessment (CGA) has shown a predictive interest in terms of mortality. The objective of our study was to assess the prognostic value of MPI for 1-year mortality in an external prospective French cohort of elderly patients with cancer.

Methods

From March 2015 to March 2017 a prospective single-center cohort study enrolled all patients with cancer, aged 75 years and older referred to the geriatric oncology clinic. We used a proportional hazard model for 1-year mortality adjusted for age, sex, tumor sites and metastatic status. C-statistics were used to assess the incremental predictive value of MPI index to these risk factors.

Results

overall, 433 patients underwent CGA with MPI (women 42%; mean age 82.8 ± 4.8 years). The most common tumor sites were prostate (23%), skin (17%), colorectum (15%) and breast (12%); 29% of patients had a metastatic disease; 231 patients (53%) belonged to the “MPI-1” group, 172 (40%) to the “MPI-2” group and 30 patients were classified in the “MPI-3” group. One-year mortality rate was 32% (23% in MPI-1, 41% in MPI-2 and 53% in MPI-3, p = 0.024). All domains of MPI except cognition and living status were significantly associated with mortality at one-year, as well as tumor sites and metastatic status. Higher MPI was associated with a higher mortality risk (adjusted HR 1.56 [95%CI 1.70–2.09] and 1.72 [1.33–2.22] for MPI groups 2 and 3 compared to 1; p < 0.0001).

Conclusions

In addition to established risk factors, MPI improves risk prediction of 1-year mortality. This practical prognostic tool may help to optimize management of these vulnerable patients.
The potential of CBC-derived ratios (monocyte-to-lymphocyte, neutrophil-to-lymphocyte, and platelet-to-lymphocyte) to predict or diagnose incident TB infection in Tanzanian adolescents
Authors: Rees Christiaan A. , Pineros Dwan B. , Amour Maryam , Munseri Patricia , Said Jamila , Magohe Albert , Matee Mecky , Pallangyo Kisali , von Reyn C. Fordham
Published: August 2020

Background

Ratios of different immune cell populations (i.e., monocyte-to-lymphocyte, neutrophil-to-lymphocyte, and platelet-to-lymphocyte ratios) have been studied as a means of predicting future tuberculosis (TB) disease risk or to assist in the diagnosis of incident TB disease. No studies to-date, however, have evaluated the potential of these ratios to predict or assist in the diagnosis of incident TB infection - the first step in the natural history of TB disease.

Methods

In this prospective study, we evaluated the complete blood count (CBC)-derived metrics of monocyte-to-lymphocyte ratio (MLR), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) as predictors of future TB infection risk or aids in the diagnosis of TB infection among 145 Tanzanian adolescents enrolled in the DAR-901 vaccine trial, using paired CBCs and interferon-gamma release assays (IGRAs) obtained at 0, 60 and 720 days after study enrollment.

Results

At baseline, there were no significant differences between study participants who remained persistently IGRA negative throughout the study period and those who subsequently converted to IGRA positive with respect to MLR (0.18 vs 0.17, p = 0.10), NLR (0.88 vs 1.02, p = 0.08), or PLR (115 vs 120, p = 0.28). Similarly, no significant differences were noted with respect to MLR, NLR, and PLR between IGRA converters and time-matched negative controls at the time of IGRA conversion. With respect to other blood cell measures, however, there were modest but significant differences between IGRA negatives and IGRA converters with respect to red blood cell count (4.8 vs 4.6 ×  106 cells/mcL, p = 0.008), hemoglobin (12.6 vs 12.3 g/dL, p = 0.01), and hematocrit (38.8 vs 37.8%, p = 0.005).

Conclusions

In contrast to prior studies that have suggested that the ratios of different immune cell populations are associated with development of TB disease, our present findings do not demonstrate an association between these ratios and the development of TB infection. However, decreased red blood cell measures were associated with the subsequent development of TB infection, suggesting either that dysregulation of iron metabolism may play a role in TB pathogenesis or that following TB infection, iron dysregulation may precede IGRA positivity.

Trial registration

Clinicaltrials.gov NCT02712424. Date of registration: March 14, 2016.
Home-based intervention for non-Hispanic black families finds no significant difference in infant size or growth: results from the Mothers & Others randomized controlled trial
Authors: Wasser Heather M. , Thompson Amanda L. , Suchindran Chirayath M. , Goldman Barbara D. , Hodges Eric A. , Heinig Meredith J. , Bentley Margaret E.
Published: August 2020

Background

Non-Hispanic black (NHB) infants are twice as likely as non-Hispanic white infants to experience rapid weight gain in the first 6 months, yet few trials have targeted this population. The current study tests the efficacy of “Mothers & Others,” a home-based intervention for NHB women and their study partners versus an attention-control, on infant size and growth between birth and 15 months.

Methods

Mothers & Others was a two-group randomized controlled trial conducted between November 2013 and December 2017 with enrollment at 28-weeks pregnancy and follow-up at 3-, 6-, 9-, 12-, and 15-months postpartum. Eligible women self-identified as NHB, English-speaking, and 18–39 years. The obesity prevention group (OPG) received anticipatory guidance (AG) on responsive feeding and care practices and identified a study partner, who was encouraged to attend home visits. The injury prevention group (IPG) received AG on child safety and IPG partners only completed study assessments. The primary delivery channel for both groups was six home visits by a peer educator (PE). The planned primary outcome was mean weight-for-length z-score. Given significant differences between groups in length-for-age z-scores, infant weight-for-age z-score (WAZ) was used in the current study. A linear mixed model, using an Intent-To-Treat (ITT) data set, tested differences in WAZ trajectories between the two treatment groups. A non-ITT mixed model tested for differences by dose received.

Results

Approximately 1575 women were screened for eligibility and 430 were enrolled. Women were 25.7 ± 5.3 years, mostly single (72.3%), and receiving Medicaid (74.4%). OPG infants demonstrated lower WAZ than IPG infants at all time points, but differences were not statistically significant (WAZdiff = − 0.07, 95% CI − 0.40 to 0.25, p = 0.659). In non-ITT models, infants in the upper end of the WAZ distribution at birth demonstrated incremental reductions in WAZ for each home visit completed, but the overall test of the interaction was not significant (F2,170 = 1.41, p = 0.25).

Conclusions

Despite rich preliminary data and a strong conceptual model, Mothers & Others did not produce significant differences in infant growth. Results suggest a positive impact of peer support in both groups.

Trial registration

ClinicalTrials.gov, NCT01938118, 09/10/2013.
Exploring patient satisfaction after operative and nonoperative treatment for midshaft clavicle fractures: a focus group analysis
Authors: Tutuhatunewa Eric D. , Stevens Martin , Dams Olivier C. , van Son Jeffrey , Louhanepessy Rebecca D. , Krabbe Paul F. M. , Postma Maarten J. , Diercks Ron L.
Published: August 2020

Background

There is no consensus on the optimal treatment for displaced midshaft clavicle fractures. Several studies indicate superior patient satisfaction in favour of operative reconstruction. It is unknown what drives superior satisfaction in this treatment group. The aim of this study was to explore patient satisfaction and identify contributors to patient satisfaction after operative and nonoperative treatment for displaced midshaft clavicle fractures in adults using a focus group approach.

Methods

Four face-to-face and two web-based focus groups were hosted. A total of 24 participants who were treated nonoperatively (n = 14) or operatively (n = 10) agreed to participate. Participants were selected using purposive sampling, ensuring variation in gender, age, treatment complications and outcomes. A question script was developed to systematically explore patient expectations, attitudes and satisfaction with different dimensions of care. All focus groups were voice-recorded and transcribed at verbatim. Thematic analysis was conducted on all face-to-face and web-based transcripts.

Results

The main emerging themes across treatment groups were; need for more information, functional recovery, speed of recovery and patient-doctor interaction. There was no difference in themes observed between operative and nonoperative focus groups. The lack of information was the most important complaint in dissatisfied patients.

Conclusion

Our study shows that informing patients about their injury, treatment options and expectations for recovery is paramount for overall patient satisfaction after treatment for a displaced midshaft clavicle fracture.

Level of evidence

Level III, focus group study.
The neglected perioperative population of undiagnosed diabetics – a retrospective cohort study
Authors: Teo Wei W. , Ti Lian K. , Lean Lyn L. , Seet Edwin , Paramasivan Ambika , Liu Weiling , Wang Jiexun , Chua Vanessa , Liew Lydia Q.
Published: August 2020

Background

Diabetes is known to increase morbidity and 30-day mortality in adults undergoing non-cardiac surgery, but longer term outcomes are less studied. This study was done to explore how undiagnosed and known diabetes affect 30-day and one-year morbidity and mortality outcomes. The secondary aim was to study the prevalence of undiagnosed diabetics in our perioperative Asian surgical population.

Methods

A retrospective cohort study of 2106 patients aged > 45 years undergoing non-cardiac surgery in a single tertiary hospital was performed. Undiagnosed diabetics were identified (HbA1c ≥6.5% or fasting blood glucose ≥126 mg/dL) and relevant demographic, clinical and surgical data were analyzed to elicit the relationship to adverse outcomes. Univariate analysis was first performed to identify significant variables with p-values ≤0.1, which were then analyzed using multiple logistic regression to calculate the adjusted odds ratio.

Results

The prevalence of undiagnosed diabetes was 7.4%. The mean and median HbA1c of known diabetics were 7.9 and 7.5%, while the mean and median HbA1c for undiagnosed diabetics were 7.2 and 6.8% respectively. 36.4% of known diabetics and 20.5% of undiagnosed diabetics respectively had a random blood glucose > 200 mg/dL. Undiagnosed diabetics had a three-fold increase in 1-year mortality compared to non-diabetics (adjusted OR 3.46(1.80–6.49) p < 0.001) but this relationship was not significant between known and non-diabetics. Compared to non-diabetics, known diabetics were at increased risks of new-onset atrial fibrillation (aOR 2.48(1.01–6.25) p = 0.047), infection (aOR 1.49(1.07–2.07) p = 0.017), 30-day readmission (aOR 1.62(1.17–2.25) p = 0.004) and 30-day mortality (aOR 3.11(1.16–8.56) p = 0.025).

Conclusions

Although undiagnosed diabetics have biochemically less severe disease compared to known diabetics at the point of testing, they are at a one-year mortality disadvantage which is not seen among known diabetics. This worrying trend highlights the importance of identifying and treating diabetes. Congruent to previous studies, known diabetics have higher morbidity and 30-day mortality compared to non-diabetics.
Sharing the initial experience of pan-cancer panel analysis in high-risk renal cell carcinoma in the Korean population
Authors: Suh Jungyo , Jeong Chang Wook , Choi Seongmin , Ku Ja Hyeon , Kim Hyeon Hoe , Kim Kwangsoo , Kwak Cheol
Published: August 2020

Background

This study aimed to assess the feasibility of a pan-cancer panel assay for high-risk renal cell carcinoma (RCC) in the Korean population. We also analyzed the clinical and genetic factors contributing to metastasis in clear cell RCC.

Methods

Thirty-one patients with advanced RCC who underwent radical nephrectomy were analyzed. A 1.8 Mb multi-cancer panel (including 25 RCC-related genes, such as VHL, PBRM1, SETD2, and MET), comprising 181 target genes, 23 fusion genes, and 45 drug target lesions developed by Seoul National University Hospital, was used for this study.

Results

We extracted DNA from 30 of the 31 (96.7%) RCC specimens. Twenty-one patients (average age 63.3 ± 11.3 years) with clear cell RCC, 5 with papillary RCC, 3 with chromophobe RCC, and one patient, each with MiT family translocation carcinoma RCC and succinate dehydrogenase deficiency RCC, were analyzed. The sequencing depth was 430.8 ± 206.6 and 97 mutations (7.3 ± 2.7 mutations per patient) were detected. The most commonly mutated genes were VHL (46%), PBRM1 (30%), and BAP1, NOTCH4, and POLQ (23.33% each). Compared with TNM stage matched data from TCGA of clear cell RCC, VHL and PBRM1 are most common in both cohorts. Univariate and multivariate analyses revealed that tumor size (Hazard ratio = 2.47, p = 0.04) and PBRM1 (Hazard ratio = 28.69, p = 0.05) were related to metastasis in clear cell RCC.

Conclusion

The pan-cancer panel comprised of RCC-related genes is a feasible and promising tool to evaluate genetic alterations in advanced RCC. However, large-scale studies and a focus on the clinical utility of this cancer panels is needed.
Outpatient dental care for people with disabilities under general anaesthesia in Switzerland
Authors: Jockusch Julia , Sobotta Bernhard A. J. , Nitschke Ina
Published: August 2020

Background

Life expectancy of people with permanent disabilities has increased. The dental care of these vulnerable patients is one of the greatest challenges for the dentist and the dental team due to limited or non-existent cooperation and the associated lack of health competence. In order to be able to provide safe and acceptable, quality dental treatment without psychological and physical stress for these patients, it is therefore necessary to resort to sedation or general anaesthesia (GA) under medical supervision. The aim of the analysis is to highlight the need for dental treatment performed under GA for people with disabilities and the associated indications and treatment patterns.

Methods

Ten-year retrospective analysis of outpatient dental care under GA for people with disabilities.

Results

Of all adult patients (n = 221) who attended the GA pre-assessment, 69.7% (n = 154) received dental treatment under GA based on the clinical findings or in cases of suspected pain. Most patients received one GA. A total of 205 dental treatment sessions were performed under GA mostly for conservative (n = 442, 52%) and surgical (n = 389, 45.8%) procedures. Endodontic treatment (n = 19, 2.2%) was rare. The failure rate related to all teeth in need of treatment (n = 850) was 5.1% (n = 43), in most cases due to secondary caries (n = 40; 93.0%). Patients were enrolled in an annual recall for dental examination and prophylaxis without GA. Non-compliant patients for whom oral hygiene was impossible received a periodic GA.

Conclusion

There is a high need of people with disabilities for dental treatment under GA. Main indications for treatment under GA are dental complaints, pain or suspected pain. Dental care can be successful if, for the benefit of patients with special needs, all carers cooperate closely. Caregivers have to be trained in nutrition control as well as in oral hygiene. These factors in conjunction help to prevent dental emergencies.
Effect of different restorative crown design and materials on stress distribution in endodontically treated molars: a finite element analysis study
Authors: Lin Jie , Lin Zhenxiang , Zheng Zhiqiang
Published: August 2020

Background

The purposes of this simulation study were to evaluate the stresses in the roots of endodontically treated molars with extensive coronal tissue loss which were restored by endocrowns (all-in-one core and crown) and traditional crowns with post-cores, during masticatory simulation using finite element analysis.

Methods

A mesio-distal cross-section of a lower right first molar was digitized and used to create 2-dimensional models of the teeth and supporting tissue; different crown designs, viz., endocrown with 2 mm occlusal clearance, endocrown with 4 mm occlusal clearance and post-core crown; different crown materials, viz., zirconia (Zr) and lithia-disilicate reinforced glass ceramic (LDRGC), and different post and core materials, viz., glass fiber (GF), stainless steel (SS) and metal cast (MC). An axial load of 600 N was applied to the central fossa of occlusal surface.

Results

The stress distributions were similar between Zr and LDRGC for periodontal ligament and alveolar bone. The root canal inner wall maximum principal stresses of SS post (70.8 MPa) and MC post (71.4 MPa) were higher than that of GF post (36.0 MPa) and endocrown (2.4 MPa).

Conclusion

The endocrowns reduced stress concentration for the root canal inner wall in comparison with the conventional post-core crown. Molars restored with endocrowns are less prone to root fracture than those with posts.
Virtual versus jaw simulation in Oral implant education: a randomized controlled trial
Authors: Zhang Baoping , Li Sihong , Gao Shuting , Hou Mingfang , Chen Hong , He Lulu , Li Yiting , Guo Yumeng , Wang Errui , Cao Rui , Cheng Jingyang , Li Ruiping , Zhang Kailiang
Published: August 2020

Background

This research aims to investigate the evaluation methods of teaching oral implant clinical courses and estimate the effectiveness of a virtual simulation platform.

Methods

Eighty second- and third-year undergraduates in Lanzhou University were recruited and randomized to either three experimental groups or one control group. The subjects undertook theoretical examinations to test their basic level of knowledge after training in similarly unified knowledge courses. Each student group then participated in an eight-hour operating training session. An operation test on pig mandible was conducted, followed by a second theoretical examination. The assessment consists of three distinct parts: a subjective operating score by a clinical senior teacher, an implant accuracy analysis in cone-beam computed tomography (angular, apical, and entrance deviation), and comparison of the two theoretical examinations. Finally, students completed a questionnaire gauging their understanding of the virtual simulation.

Results

There was no significant difference between the four groups in first theoretical examination (P > 0.05); the second theoretical scores of the V-J and J-V group (62.90 ± 3.70, 60.05 ± 2.73) were significantly higher than the first time (57.05 ± 3.92, P < 0.05), while no difference between the V (57.10 ± 3.66) and J (56.89 ± 2.67) groups was found. Thus, the combination of V-J was effective in improving students’ theoretical scores. The V-J and J-V groups had higher scores on operation (73.98 ± 4.58, 71.85 ± 4.67) and showed better implant precision.

Conclusion

Virtual simulation education, especially with a jaw simulation model, could improve students’ implantology achievements and training. Currently study found that the V-J group may performed better than the J-V group in oral implant teaching.
Pharmacy students’ attitudes toward patient safety in Saudi Arabia: a cross-sectional study
Authors: Alwhaibi Monira , AlRuthia Yazed , Almalag Haya , Alkofide Hadeel , Balkhi Bander , Almejel Amani , Alshammari Fahad
Published: August 2020

Background

There is a growing recognition of the importance of teaching patient safety to medical students to improve healthcare and minimize patients’ harm; however, few studies evaluated the attitudes of pharmacy students toward patient safety. The purpose of this study was to explore the attitudes toward patient safety among pharmacy students in Saudi Arabia.

Methods

A cross-sectional study was conducted among pharmacy students from four different universities using a self-administered questionnaire. The Attitudes to Patient Safety Questionnaire III (APSQ-III) was used to measure the attitude toward patient safety. The data were presented using descriptive statistics, such as percentages and means, and compared across gender using Student’s t-test.

Results

All of the students who agreed to participate and signed the consent form have completed the questionnaire. Of the 347 pharmacy students who participated in the study; 63% were enrolled in the Doctor of Pharmacy Program and 37% were enrolled in the Bachelor of Pharmaceutical Sciences program. Only 46% of the participants received courses for patient safety mainly in the fourth year of their pharmacy program, and around 93% were interested to learn more about patient safety. A more positive attitude toward patient safety was reported in the domain of ‘confidence to report errors’, ‘working hours as error cause’, ‘patient involvement in reducing error’, and ‘team functioning’. However, most negative attitudes were reported in the domains of ‘Error inevitability’ and ‘Disclosure responsibility’. Gender differences were noticed in the attitude toward patient safety; female students had more positive attitudes in most domains of patient safety.

Conclusions

Around one-half of the surveyed pharmacy students did not receive any courses on patient safety. Our findings emphasize the need for including patient safety courses in the curricula of the different pharmacy programs given the patient safety training importance in improving the quality of patient care.
Comparative transcriptome analysis of Parkinson’s disease and Hutchinson-Gilford progeria syndrome reveals shared susceptible cellular network processes
Authors: Hendrickx Diana M. , Glaab Enrico
Published: August 2020

Background

Parkinson’s Disease (PD) and Hutchinson-Gilford Progeria Syndrome (HGPS) are two heterogeneous disorders, which both display molecular and clinical alterations associated with the aging process. However, similarities and differences between molecular changes in these two disorders have not yet been investigated systematically at the level of individual biomolecules and shared molecular network alterations.

Methods

Here, we perform a comparative meta-analysis and network analysis of human transcriptomics data from case-control studies for both diseases to investigate common susceptibility genes and sub-networks in PD and HGPS. Alzheimer’s disease (AD) and primary melanoma (PM) were included as controls to confirm that the identified overlapping susceptibility genes for PD and HGPS are non-generic.

Results

We find statistically significant, overlapping genes and cellular processes with significant alterations in both diseases. Interestingly, the majority of these shared affected genes display changes with opposite directionality, indicating that shared susceptible cellular processes undergo different mechanistic changes in PD and HGPS. A complementary regulatory network analysis also reveals that the altered genes in PD and HGPS both contain targets controlled by the upstream regulator CDC5L.

Conclusions

Overall, our analyses reveal a significant overlap of affected cellular processes and molecular sub-networks in PD and HGPS, including changes in aging-related processes that may reflect key susceptibility factors associated with age-related risk for PD.