bluuebunny/crossref_metadata_2025 huggingface dataset:
Metabolic profiling reveals interleukin-17A monoclonal antibody treatment ameliorate lipids metabolism with the potentiality to reduce cardiovascular risk in psoriasis patients
Authors: Cao Han , Su Shengmin , Yang Qi , Le Yunchen , Chen Lihong , Hu Mengyan , Guo Xiaoyu , Zheng Jie , Li Xia , Yu Yunqiu
Published: February 2021

Background

Psoriasis is a common chronic inflammatory skin disease associated with overproduction of interleukin-17A (IL-17A). IL-17A monoclonal antibodies (mAbs) have shown clinical efficacy in psoriasis patients. Although a series of different overlapping mechanisms have been found to establish a link between psoriasis and cardiovascular diseases, the underlying mechanisms of the two types of diseases and the potential efficacy of IL-17A mAbs in amelioration of cardiovascular comorbidities remain unclear.

Methods

Serum samples from two study cohorts including 117 individuals were analyzed using a high-throughput UHPLC-MS platform. Non-targeted metabolic profiling analysis was first conducted with samples from 28 healthy individuals and from 28 psoriasis patients before and after 12-weeks of ixekizumab treatment in study cohort 1. Study cohort 2 was additionally recruited to validate the correlations of the identified metabolites with cardiovascular diseases.

Results

A total of 43 differential metabolites, including lysophospholipids, free fatty acids, acylcarnitines and dicarboxylic acids, were accurately identified in study cohort 1, and the analysis showed that lipid metabolism was impaired in psoriasis patients. Compared with healthy individuals, psoriasis patients had higher levels of lysophosphatidylcholines, lysophosphatidylinositols, lysophosphatidic acids and free fatty acids, but lower levels of acylcarnitines and dicarboxylic acids. The identified dicarboxylic acid levels were inversely correlated with psoriasis area and severity index (PASI) scores (P < 0.05). The results for study cohort 2 were largely consistent with the results for study cohort 1. Moreover, the levels of all identified lysophosphatidylcholines were higher in psoriasis patients with coronary heart diseases than in psoriasis without coronary heart disease. Notably, most of these lipidic changes were ameliorated by ixekizumab treatment.

Conclusion

The results of this non-targeted metabolomic analysis indicate that treatment with IL-17A mAbs can not only ameliorate psoriasis lesions but also restore dysregulated lipid metabolism to normal levels in psoriasis patients. Considering that dysregulated lipid metabolism has been regarded as the critical factor in cardiovascular diseases, the recovery of lipid metabolites in psoriasis patients indicates that IL-17A mAbs might have the potential protective effects against cardiovascular comorbidities.
Sequential vs concurrent adjuvant chemotherapy of anthracycline and taxane for operable breast cancer
Authors: Chen Wanjing , Tu Qian , Shen Yanfei , Tang Kejun , Hong Mengying , Shen Yong
Published: February 2021

Background

Whether a sequential or concurrent regimen of anthracyclines and taxanes is superior for breast cancer is controversial. We compared the efficacy of two regimens in patients with operable breast cancer based on all relevant published data of phase III randomized controlled trials.

Methods

A comprehensive literature search on PubMed, Web of Science, Embase, ScienceDirect, Google Scholar, and ClinicalTrials.gov databases was performed up to May 2020. Meta-analysis was performed to evaluate the different efficacy on disease-free survival (DFS) and overall survival (OS) for the two chemotherapy regimens. Subgroup analyses were further carried out in terms of node status and anthracycline selection.

Results

Compared to the concurrent regimen, the sequential regimen did not improve the DFS or OS in the population studied. Subgroup analysis showed that in node-positive patients, the sequential regimen had better DFS, but not OS, than the concurrent regimen. In sequential regimen, patients who received doxorubicin and taxanes had improved DFS and OS than patients who were administered epirubicin and taxanes. Furthermore, for patients who received doxorubicin and taxanes, compared to the sequential regimen, fewer cycles (4 cycles) of concurrent treatment resulted in a worse DFS and OS, which can be rescued by more cycles (6 cycles).

Conclusions

The sequential regimen of anthracyclines and taxanes for patients with operable breast cancer did not yield a significant benefit in DFS or OS over the concurrent regimen. The sequential regimen, however, provided a better DFS than concurrent regimen for node-positive patients. Interestingly, further subgroup analysis showed that for node-positive patients who were given doxorubicin and taxanes, more cycles (6 cycles) of the concurrent regimen may rescue the efficacy for fewer cycles (4 cycles).
Does the Endoscopic Surgical Skill Qualification System improve patients’ outcome following laparoscopic surgery for colon cancer? A multicentre, retrospective analysis with propensity score matching
Authors: Kazama Keisuke , Numata Masakatsu , Aoyama Toru , Atsumi Yosuke , Tamagawa Hiroshi , Godai Teni , Saeki Hiroyuki , Saigusa Yusuke , Shiozawa Manabu , Yukawa Norio , Masuda Munetaka , Rino Yasushi
Published: February 2021

Background

This study aimed to investigate the short-term and oncological impact of the Endoscopic Surgical Skill Qualification System (ESSQS) by the Japan Society for Endoscopic Surgery on the operator performing laparoscopic surgery for colon cancer.

Methods

This retrospective cohort study was based on medical records from a multicentre database. A total of 417 patients diagnosed with stage II/III colon and rectosigmoid cancer treated with curative resection were divided into two groups according to whether they were operated on by qualified surgeons (Q group, n=352) or not (NQ group, n=65). Through strict propensity score matching, 98 cases (49 in each group) were assessed.

Results

Operative time was significantly longer in the NQ group than in the Q group (199 vs. 168 min, p=0.029). The amount of blood loss, post-operative complications, and duration of hospitalisation were similar between both groups. No mortality was observed. One conversion case was seen in the NQ group. The 3-year recurrence-free survival rate was 86.6% in the NQ group and 88.2% in the Q group, which was not statistically significant (log-rank p=0.966).

Conclusion

Direct operation by ESSQS-qualified surgeons contributed to a shortened operation time. Under an organised educational environment, almost equivalent safety and oncological outcomes are expected regardless of the surgeon’s qualifications.
Tumor immunogenomic signatures improve a prognostic model of melanoma survival
Authors: Morales Leah , Simpson Danny , Ferguson Robert , Cadley John , Esteva Eduardo , Monson Kelsey , Chat Vylyny , Martinez Carlos , Weber Jeffrey , Osman Iman , Kirchhoff Tomas
Published: February 2021

Background

Tumor mutation burden (TMB) has been associated with melanoma immunotherapy (IT) outcomes, including survival. We explored whether combining TMB with immunogenomic signatures recently identified by The Cancer Genome Atlas (TCGA) can refine melanoma prognostic models of overall survival (OS) in patients not treated by IT.

Methods

Cox proportional-hazards (Cox PH) analysis was performed on 278 metastatic melanomas from TCGA not treated by IT. In a discovery and two validation cohorts Cox PH models assessed the interaction between TMB and 53 melanoma immunogenomic features to refine prediction of melanoma OS.

Results

Interferon-γ response (IFNγRes) and macrophage regulation gene signatures (MacReg) combined with TMB significantly associated with OS (p = 8.80E−14). We observed that patients with high TMB, high IFNγRes and high MacReg had significantly better OS compared to high TMB, low IFNγRes and low MacReg (HR = 2.8, p = 3.55E−08). This association was not observed in low TMB patients.

Conclusions

We report a model combining TMB and tumor immune features that significantly improves prediction of melanoma OS, independent of IT. Our analysis revealed that patients with high TMB, high levels of IFNγRes and MacReg had significantly more favorable OS compared to high TMB patients with low IFNγRes and low MacReg. These findings may substantially improve current melanoma prognostic models.
Chimeric antigen receptor T cells engineered to secrete CD40 agonist antibodies enhance antitumor efficacy
Authors: Zhang Yajun , Wang Pei , Wang Tengjiao , Fang Yuan , Ding Yongmei , Qian Qijun
Published: February 2021

Background

Although chimeric antigen receptor (CAR)-T cell therapy has been remarkably successful for haematological malignancies, its efficacy against solid tumors is limited. The combination of CAR-T cell therapy with immune checkpoint inhibitors (CPIs), such as PD-1, PD-L1, and CTLA-4 antibodies, is a promising strategy for enhancing the antitumor efficacy of CAR-T cells. However, because most patients acquire resistance to CPIs, investigating other strategies is necessary to further improve the antitumor efficacy of CAR-T cell therapy for solid tumors. Recently, CD40 agonist antibodies showed potential antitumor efficacy by activating the CD40 pathway.

Results

Based on the piggyBac transposon system, rather than the widely used viral vectors, we constructed a meso3-CD40 CAR-T targeting region III of mesothelin (MSLN) that possessed the ability to secrete anti-CD40 antibodies. Compared with meso3 CAR-T cells, which did not secrete the anti-CD40 antibody, meso3-CD40 CAR-T cells secreted more cytokines and had a relatively higher proportion of central memory T (TCM) cells after stimulation by the target antigen. In addition, compared with meso3 CAR-T cells, meso3-CD40 CAR-T cells had a more powerful cytotoxic effect on target cells at a relatively low effector-to-target ratio. More importantly, we demonstrated that the antitumor activity of meso3-CD40 CAR-T cells was enhanced in a human ovarian cancer xenograft model in vivo.

Conclusions

In conclusion, these results highlight anti-CD40-secreting CAR-T cells generated by nonviral vectors as a potential clinical strategy for improving the efficacy of CAR-T cell therapies.
Platelets and lymphocytes drive progressive penumbral tissue loss during middle cerebral artery occlusion in mice
Authors: Schuhmann Michael K. , Bieber Michael , Franke Maximilian , Kollikowski Alexander M. , Stegner David , Heinze Katrin G. , Nieswandt Bernhard , Pham Mirko , Stoll Guido
Published: February 2021

Background

In acute ischemic stroke, cessation of blood flow causes immediate tissue necrosis within the center of the ischemic brain region accompanied by functional failure in the surrounding brain tissue designated the penumbra. The penumbra can be salvaged by timely thrombolysis/thrombectomy, the only available acute stroke treatment to date, but is progressively destroyed by the expansion of infarction. The underlying mechanisms of progressive infarction are not fully understood.

Methods

To address mechanisms, mice underwent filament occlusion of the middle cerebral artery (MCAO) for up to 4 h. Infarct development was compared between mice treated with antigen-binding fragments (Fab) against the platelet surface molecules GPIb (p0p/B Fab) or rat immunoglobulin G (IgG) Fab as control treatment. Moreover, Rag1−/− mice lacking T-cells underwent the same procedures. Infarct volumes as well as the local inflammatory response were determined during vessel occlusion.

Results

We show that blocking of the platelet adhesion receptor, glycoprotein (GP) Ibα in mice, delays cerebral infarct progression already during occlusion and thus before recanalization/reperfusion. This therapeutic effect was accompanied by decreased T-cell infiltration, particularly at the infarct border zone, which during occlusion is supplied by collateral blood flow. Accordingly, mice lacking T-cells were likewise protected from infarct progression under occlusion.

Conclusions

Progressive brain infarction can be delayed by blocking detrimental lymphocyte/platelet responses already during occlusion paving the way for ultra-early treatment strategies in hyper-acute stroke before recanalization.
Transcriptome profiling of long noncoding RNAs and mRNAs in spinal cord of a rat model of paclitaxel-induced peripheral neuropathy identifies potential mechanisms mediating neuroinflammation and pain
Authors: Li Yuanyuan , Yin Chengyu , Liu Boyu , Nie Huimin , Wang Jie , Zeng Danyi , Chen Ruixiang , He Xiaofen , Fang Junfan , Du Junying , Liang Yi , Jiang Yongliang , Fang Jianqiao , Liu Boyi
Published: February 2021

Background

Paclitaxel is a widely prescribed chemotherapy drug for treating solid tumors. However, paclitaxel-induced peripheral neuropathy (PIPN) is a common adverse effect during paclitaxel treatment, which results in sensory abnormalities and neuropathic pain among patients. Unfortunately, the mechanisms underlying PIPN still remain poorly understood. Long noncoding RNAs (lncRNAs) are novel and promising targets for chronic pain treatment, but their involvement in PIPN still remains unexplored.

Methods

We established a rat PIPN model by repetitive paclitaxel application. Immunostaining, RNA sequencing (RNA-Seq) and bioinformatics analysis were performed to study glia cell activation and explore lncRNA/mRNA expression profiles in spinal cord dorsal horn (SCDH) of PIPN model rats. qPCR and protein assay were used for further validation.

Results

PIPN model rats developed long-lasting mechanical and thermal pain hypersensitivities in hind paws, accompanied with astrocyte and microglia activation in SCDH. RNA-Seq identified a total of 814 differentially expressed mRNAs (DEmRNA) (including 467 upregulated and 347 downregulated) and 412 DElncRNAs (including 145 upregulated and 267 downregulated) in SCDH of PIPN model ratsvs. control rats. Functional analysis of DEmRNAs and DElncRNAs identified that the most significantly enriched pathways include immune/inflammatory responses and neurotrophin signaling pathways, which are all important mechanisms mediating neuroinflammation, central sensitization, and chronic pain. We further compared our dataset with other published datasets of neuropathic pain and identified a core set of immune response-related genes extensively involved in PIPN and other neuropathic pain conditions. Lastly, a competing RNA network analysis of DElncRNAs and DEmRNAs was performed to identify potential regulatory networks of lncRNAs on mRNA through miRNA sponging.

Conclusions

Our study provided the transcriptome profiling of DElncRNAs and DEmRNAs and uncovered immune and inflammatory responses were predominant biological events in SCDH of the rat PIPN model. Thus, our study may help to identify promising genes or signaling pathways for PIPN therapeutics.
Contraceptive use and maternal mortality in Indonesia: a community-level ecological analysis
Authors: Aryanty Riznawaty Imma , Romadlona NohanArum , Besral Besral , Panggabean Elvi Debora P. , Utomo Budi , Makalew Richard , Magnani Robert J.
Published: February 2021

Background

Prior studies have shown that contraceptive use reduces maternal mortality independently of other maternal health services. The present study took advantage of geographically detailed Indonesian data to study the interplay between contraceptive use and other risk and protective factors for maternal mortality at the community level, a level of analysis where the protective effects of family planning can be best understood.

Methods

Data from the 2015 Intercensal Population Survey (SUPAS) and the 2014 Village Potential Survey (PODES) were used to construct a series of census block-level variables measuring key risk and protective factors for maternal mortality. The relationships between these factors and maternal mortality, measured via natural log-transformation of past five-year maternal mortality ratios in each of the 40,748 census blocks were assessed via log-linear regressions.

Results

Higher community maternal mortality ratios were associated with lower community contraceptive prevalence, higher percentage of parity four-plus births, higher proportion of poor households, lower population density of hospitals, higher density of traditional birth attendants (TBA), and residence outside of Java-Bali. For every percentage point increase in CPR, community maternal mortality ratios were lower by 7.0 points (95% CI = 0.9, 14.3). Community-level household wealth was the strongest predictor of maternal mortality.

Conclusions

Community contraceptive prevalence made a significant contribution to reducing maternal mortality net of other risk and protective factors during 2010–2015. Increased health system responsiveness to the needs of pregnant women and reductions in socioeconomic and geographic disparities in maternal health services will be needed for Indonesia to reach the 2030 SDG maternal mortality goal.
Catatonia associated with late-life psychosis successfully treated with lithium: a case report
Authors: Sugawara Hiroko , Takamatsu Junpei , Hashimoto Mamoru , Ikeda Manabu
Published: February 2021

Background

Catatonia is a psychomotor syndrome that presents various symptoms ranging from stupor to agitation, with prominent disturbances of volition. Its pathogenesis is poorly understood. Benzodiazepines and electroconvulsive therapy (ECT) are safe and effective standard treatments for catatonia; however, alternative treatment strategies have not been established in cases where these treatments are either ineffective or unavailable. Here, we report a case of catatonia associated with late-life psychosis, which was successfully treated with lithium.

Case presentation

A 66-year-old single man with hearing impairment developed hallucination and delusions and presented with catatonic stupor after a fall. He initially responded to benzodiazepine therapy; however, his psychotic symptoms became clinically evident and benzodiazepine provided limited efficacy. Blonanserin was ineffective, and ECT was unavailable. His catatonic and psychotic symptoms were finally relieved by lithium monotherapy.

Conclusions

Catatonic symptoms are common in patients with mood disorders, suggesting that lithium may be effective in these cases. Moreover, lithium may be effective for both catatonic and psychotic symptoms, as it normalizes imbalances of excitatory and inhibitory systems in the brain, which underlies major psychosis. Cumulative evidence from further cases is needed to validate our findings.
Social capital and chemsex initiation in young gay, bisexual, and other men who have sex with men: the pink carpet Y cohort study
Authors: Tan Rayner Kay Jin , O’Hara Caitlin Alsandria , Koh Wee Ling , Le Daniel , Tan Avin , Tyler Adrian , Tan Calvin , Kwok Chronos , Banerjee Sumita , Wong Mee Lian
Published: February 2021

Background

Young gay, bisexual, and other men who have sex with men (YMSM) are especially vulnerable to the risks associated with sexualized substance use, or ‘chemsex’. Engaging in chemsex established as a major risk factor for Human Immunodeficiency Virus (HIV) acquisition, and is thus a public health issue of increasing urgency. This paper attempts to explore the association between measures of social capital and patterns of sexualized substance use among a sample of YMSM in Singapore.

Methods

Results of this study were derived from baseline data of the Pink Carpet Y Cohort Study in Singapore, comprising a sample of 570 HIV-negative YMSM aged 18 to 25 years old. Latent class analysis was employed to identify classes with similar patterns of sexualized substance use, and multinomial logistic regression was employed to examine associations between class membership and proxy measures of social capital, including age of sexual debut, bonding and bridging social capital, connectedness to the lesbian, gay, bisexual and transgender community, and outness.

Results

Latent class analysis revealed three classes of YMSM based on their histories of sexualized substance use, which we labelled as ‘alcohol’, ‘poppers’, and ‘chemsex’. Multivariable analyses revealed that participants who were older (aOR = 1.19,p = 0.002) and who identified as gay (aOR = 2.43, p = 0.002) were more likely to be in the poppers class compared to the alcohol class. Participants with a later age of sexual debut were increasingly less likely to be in the poppers (aOR = 0.93,p = 0.039) and chemsex classes (aOR = 0.85,p = 0.018), compared to the alcohol class.

Conclusions

Varying measures of social capital such as an earlier age of exposure to sexual networks may predispose YMSM to greater opportunities for sexualized substance use. Future interventions should target YMSM who become sexually active at an earlier age to reduce the risks associated with sexualized substance use.
Transdiaphragmatic single-port video-assisted thoracoscopic surgery; a novel approach for pulmonary metastasectomy through laparotomy incision – case series
Authors: Abdel Jalil Riad , Abou Chaar Mohamad K. , Shihadeh Omar M. , Al-Qudah Obada , Gharaibeh Azza , Aldimashki Loulia , Dabous Ali , Ghanem Rami , Al-Edwan Ahed
Published: February 2021

Background

Pulmonary metastasectomy was performed in the early twentieth century and ever since, it has evolved to be one of the main treatment options for certain metastatic malignancies. The advancement of minimally invasive procedures enabled new techniques to minimize morbidity and improve patient quality of care and overall outcome.

Cases presentation

Herein we present three patients, aged 53, 48, and 27 years, known to have sigmoid, rectal, and non-seminomatous germ cell tumors respectively. All patients were diagnosed to have metastatic lung nodules and underwent laparotomy to excise abdominal tumors followed by trans-diaphragmatic single-port video-assisted thoracoscopic pulmonary metastasectomy. All patients achieved complete surgical tumor excision, and none had pulmonary related complications on follow-up.

Conclusion

Our prescribed novel trans-diaphragmatic single-port video-assisted thoracoscopic surgery (VATS) technique for synchronous pulmonary metastasectomy and intra-abdominal tumor resection is safe and can achieve complete resection with negative margins.
U-IMD: the first Unified European registry for inherited metabolic diseases
Authors: Opladen Thomas , Gleich Florian , Kozich Viktor , Scarpa Maurizio , Martinelli Diego , Schaefer Franz , Jeltsch Kathrin , Juliá-Palacios Natalia , García-Cazorla Ángels , Dionisi-Vici Carlo , Kölker Stefan
Published: February 2021

Background

Following the broad application of new analytical methods, more and more pathophysiological processes in previously unknown diseases have been elucidated. The spectrum of clinical presentation of rare inherited metabolic diseases (IMDs) is broad and ranges from single organ involvement to multisystemic diseases. With the aim of overcoming the limited knowledge about the natural course, current diagnostic and therapeutic approaches, the project has established the first unified patient registry for IMDs that fully meets the requirements of the European Infrastructure for Rare Diseases (ERDRI).

Results

In collaboration with the European Reference Network for Rare Hereditary Metabolic Disorders (MetabERN), the Unified European registry for Inherited Metabolic Diseases (U-IMD) was established to collect patient data as an observational, non-interventional natural history study. Following the recommendations of the ERDRI the U-IMD registry uses common data elements to define the IMDs, report the clinical phenotype, describe the biochemical markers and to capture the drug treatment. Until today, more than 1100 IMD patients have been registered.

Conclusion

The U-IMD registry is the first observational, non-interventional patient registry that encompasses all known IMDs. Full semantic interoperability for other registries has been achieved, as demonstrated by the use of a minimum common core data set for equivalent description of metabolic patients in U-IMD and in the patient registry of the European Rare Kidney Disease Reference Network (ERKNet). In conclusion, the U-IMD registry will contribute to a better understanding of the long-term course of IMDs and improved patients care by understanding the natural disease course and by enabling an optimization of diagnostic and therapeutic strategies.
Circulating cell‐free epstein–barr virus DNA levels and clinical features in Moroccan patients with nasopharyngeal carcinoma
Authors: Gihbid Amina , Benzeid Raja , Faouzi Abdellah , Nourlil Jalal , Tawfiq Nezha , Benchakroun Nadia , Guensi Amal , Bendahhou Karima , Benider Abdellatif , El Benna Naima , Chaoui Imane , Cadi Rachida , Mzibri Mohammed El , Khyatti Meriem
Published: February 2021

Background

The identification of effective prognosis biomarkers for nasopharyngeal carcinoma (NPC) is crucial to improve treatment and patient outcomes. In the present study, we have attempted to evaluate the correlation between pre-treatment plasmatic Epstein-Barr virus (EBV) DNA load and the conventional prognostic factors in Moroccan patients with NPC.

Methods

The present study was conducted on 121 histologically confirmed NPC patients, recruited from January 2017 to December 2018. Circulating levels of EBV DNA were measured before therapy initiation using real-time quantitative PCR.

Results

Overall, undifferentiated non-keratinizingcarcinoma type was the most common histological type (90.1 %), and 61.8 % of patients were diagnosed at an advanced disease stage (IV). Results of pre-treatment plasma EBV load showed that 90.9 % of patients had detectable EBV DNA, with a median plasmatic viral load of 7710 IU/ml. The correlation between pre-treatment EBV DNA load and the conventional prognostic factors showed a significant association with patients’ age (p = 0.01), tumor classification (p = 0.01), lymph node status (p = 0.003), metastasis status (p = 0.00) and overall cancer stage (p = 0.01). Unexpectedly, a significant higher level of pre-treatment EBV DNA was also found in plasma of NPC patients with a family history of cancer (p = 0.04). The risk of NPC mortality in patients with high pretreatment EBVDNA levels was significantly higher than that of those with low pre-treatment plasma EBV-DNA levels (p < 0.05). Furthermore, patients with high pre-treatment EBV-DNA levels (≥ 2000, ≥ 4000) had a significant low overall survival (OS) rates (p < 0.05). Interestingly, lymph node involvement, metastasis status and OS were found to be the most important factors influencing the EBV DNA load in NPC patients.

Conclusions

The results of the present study clearly showed a high association between pre-treatment EBV DNA load, the crucial classical prognostic factors (T, N, M and disease stage) of NPC and OS, suggesting that pre-treatment EBV DNA can be a useful prognostic biomarker in clinical decision-making and improving NPC treatment in Morocco.
A 12-year retrospective evaluation of anal pre-cancerous lesions and cancer in people living with HIV-1 infection in the Southeastern U.S
Authors: Ye Yuanfan , Burkholder Greer A. , Mukherjee Amrita , Chu Daniel , Bansal Anju , Sudenga Staci L. , Junkins Anna , Al Diffalha Sameer , Saag Michael S. , Shrestha Sadeep
Published: February 2021

Background

Anal cancer is rare in the general population in both genders in the US, but an increased incidence of anal cáncer (AC) has been reported among people living with HIV-1 infection (PLWH) and little is known among the population in South US.

Methods

In a retrospective study design, electronic health records from 2006 to 2018 were reviewed in a HIV clinical cohort at the University of Alabama at Birmingham. Associations of demographic, sociodemographic, and HIV-clinical indicators were examined in univariate analyses between high-grade squamous intraepithelial lesions (HSIL) and AC cases and condition-free individuals. Factors for anal/rectal cytology screening tests among PLWH were also assessed over time. Ages at onset of anal cancer were compared with the general US population reported by the National Surveillance, Epidemiology, and End Results Program.

Results

A total of 79 anal HSIL (96% men) and 43 cancer (100% men) patients were observed along with 4367 HSIL/cancer-free patients (75.9% men). HSIL (P < 0.0001) and AC (0.0001 < P < 0.01) were associated with being men who have sex with men (MSM). An incidence of 258 per 100,000 person-year was observed among this clinical cohort of PLWH. PLWH who were 45–54 years appeared to be at highest risk of AC (58.1%), as compared to those 55–64 years in the general population. Overall, 79% of PLWH anal cancers were diagnosed among those under 55 years (vs 39.5% in general population) indicating early onset of AC. In total 29.1% of HSIL and 44.2% of AC patients had not received an anal/rectal cytology examination 1 year prior to diagnosis.

Conclusion

AC incidence among HIV-infected men was 161 times higher than general population with an earlier age of onset/diagnosis. Many patients with AC had missed screening opportunities that could potentially have captured neoplasia in pre-cancerous stages. AC-related screening guidelines need to be integrated into routine clinical care, especially among PLWH at highest risk such as MSM and those with lower CD4 counts.
Fertility care amidst the COVID19 pandemic: the American experience
Authors: Schirmer Austin D. , Kawwass Jennifer F. , Adashi Eli Y.
Published: February 2021

The COVID-19 pandemic has claimed the lives of over one million people worldwide, and has affected all aspects of healthcare worldwide, including the delivery of care to patients with fertility-related diagnoses. In the United States, the response of US fertility clinics to the COVID-19 pandemic was coordinated by the American Society for Reproductive Medicine (ASRM). ASRM acted quickly to develop guidelines for limiting fertility treatment and clinic consultations during the early days of the pandemic, and then safely restarting fertility treatment. A survey of patients with fertility-related diagnoses who presented for care during the first months of the pandemic revealed that a majority of patients who presented for care during the early months of the pandemic experienced delayed or cancelled treatment cycles. Patients with infertility subsequently reported a desire to resume fertility care, but emphasized the importance of their clinic having policies and procedures in place to limit the risk of infection.
Retraction Note: The role of apatinib combined with paclitaxel (aluminum binding type) in platinum-resistant ovarian cancer
Authors: Zhao Hong , Li Rong , Wang Xiaoyan , Lu Xin , Hu Min , Zhang Jinbin , Zhao Xia , Song Xiaoqin , Liu Yangyang
Published: February 2021

This article has been retracted. Please see the Retraction Notice for more detail: https://doi.org/10.1186/s13048-021-00785-1.
Abnormalities of early folliculogenesis and serum anti-Müllerian hormone in chinese patients with polycystic ovary syndrome
Authors: Du Juan , Ruan Xiangyan , Jin Fengyu , Li Yanglu , Cheng Jiaojiao , Gu Muqing , Mueck Alfred Otto
Published: February 2021

Purpose

To investigate abnormalities of early folliculogenesis and Anti-Müllerian hormone (AMH) concentrations in polycystic ovary syndrome (PCOS) patients, and to analyze the association between AMH and early-stage follicle densities (FD).

Methods

A total of 175 patients underwent ovarian tissue cryopreservation in the first official cryobank in China, of which 16 patients aged 30–40 years old were diagnosed with endometrial cancer (all without initial chemo/radiotherapy), including 5 patients with concurrent PCOS and the other 11 patients without. We obtained standard cortical biopsies to measure FD using calcein staining. Blood samples were collected before cryopreservation to evaluate AMH concentrations.

Results

PCOS showed nearly three times the primordial and primary FD than NPCOS (P = 0.027), as well as more secondary preantral follicles (P = 0.002). A significantly higher proportion of secondary preantral follicles and a lower proportion of primordial and primary follicles were observed in PCOS (P = 0.01). Furthermore, the AMH concentration in PCOS was four times higher than that in NPCOS (P = 0.003), which is significantly correlated with primordial and primary follicle densities (r = 0.855, P < 0.001) and secondary preantral follicle densities (r = 0.732, P = 0.007).

Conclusions

We found significant disorders of early folliculogenesis in PCOS, which showed close correlation with increased AMH concentrations. To our knowledge, abnormalities of early-stage follicles have been shown for the first time in ovarian tissue of Chinese PCOS women. We suppose that the elevated AMH level is associated with abnormalities of early folliculogenesis within the complex PCOS pathogenesis, which may explain why AMH has the potential to be used as a biomarker for the diagnosis of PCOS. Our findings provide more implications for understanding the mechanism of PCOS, and new directions for further studies.
Does high dose intravenous acetaminophen affect liver function for PDA closure in premature neonate?
Authors: Bahrami Reza , Ezzatabadi Aida , Mehdizadegan Nima , Mohammadi Hamid , Amoozgar Hamid , Edraki Mohammadreza
Published: February 2021

Objectives

The aim of this study was to collect consistent data on the efficacy and safety and evaluation hepatotoxicity of intravenous acetaminophen for the treatment of PDA in preterm infants.

Methods

This is an observational longitudinal prospective study on 46 preterm infants with PDA who treated with high dose of acetaminophen and evaluated with echocardiography and serum liver enzymes at Hafez and Zeinabiyeh hospitals from January 2016 to December 2019.

Result

Forty-six preterm infants with PDA treated with intravenous acetaminophen. Rate of closure of PDA was 82.6. There was no significant difference after treatment regarding AST, ALT, Albumin, total and direct bilirubin (P value > 0.05) and no adverse side effects were observed in association with intravenous acetaminophen.

Conclusion

High dose of acetaminophen is not more effective than that with standard doses although without hepatotoxic side effect for PDA closure.
Distinct mechanisms of resistance to fulvestrant treatment dictate level of ER independence and selective response to CDK inhibitors in metastatic breast cancer
Authors: Kaminska Kamila , Akrap Nina , Staaf Johan , Alves Carla L. , Ehinger Anna , Ebbesson Anna , Hedenfalk Ingrid , Beumers Lukas , Veerla Srinivas , Harbst Katja , Ehmsen Sidse , Borgquist Signe , Borg Åke , Pérez-Fidalgo Alejandro , Ditzel Henrik J. , Bosch Ana , Honeth Gabriella
Published: February 2021

Background

Resistance to endocrine treatment in metastatic breast cancer is a major clinical challenge. Clinical tools to predict both drug resistance and possible treatment combination approaches to overcome it are lacking. This unmet need is mainly due to the heterogeneity underlying both the mechanisms involved in resistance development and breast cancer itself.

Methods

To study the complexity of the mechanisms involved in the resistance to the selective estrogen receptor degrader (SERD) fulvestrant, we performed comprehensive biomarker analyses using several in vitro models that recapitulate the heterogeneity of developed resistance. We further corroborated our findings in tissue samples from patients treated with fulvestrant.

Results

We found that different in vitro models of fulvestrant resistance show variable stability in their phenotypes, which corresponded with distinct genomic alterations. Notably, the studied models presented adaptation at different cell cycle nodes to facilitate progression through the cell cycle and responded differently to CDK inhibitors. Cyclin E2 overexpression was identified as a biomarker of a persistent fulvestrant-resistant phenotype. Comparison of pre- and post-treatment paired tumor biopsies from patients treated with fulvestrant revealed an upregulation of cyclin E2 upon development of resistance. Moreover, overexpression of this cyclin was found to be a prognostic factor determining resistance to fulvestrant and shorter progression-free survival.

Conclusions

These data highlight the complexity of estrogen receptor positive breast cancer and suggest that the development of diverse resistance mechanisms dictate levels of ER independence and potentially cross-resistance to CDK inhibitors.
LINE retrotransposons characterize mammalian tissue-specific and evolutionarily dynamic regulatory regions
Authors: Roller Maša , Stamper Ericca , Villar Diego , Izuogu Osagie , Martin Fergal , Redmond Aisling M. , Ramachanderan Raghavendra , Harewood Louise , Odom Duncan T. , Flicek Paul
Published: February 2021

Background

To investigate the mechanisms driving regulatory evolution across tissues, we experimentally mapped promoters, enhancers, and gene expression in the liver, brain, muscle, and testis from ten diverse mammals.

Results

The regulatory landscape around genes included both tissue-shared and tissue-specific regulatory regions, where tissue-specific promoters and enhancers evolved most rapidly. Genomic regions switching between promoters and enhancers were more common across species, and less common across tissues within a single species. Long Interspersed Nuclear Elements (LINEs) played recurrent evolutionary roles: LINE L1s were associated with tissue-specific regulatory regions, whereas more ancient LINE L2s were associated with tissue-shared regulatory regions and with those switching between promoter and enhancer signatures across species.

Conclusions

Our analyses of the tissue-specificity and evolutionary stability among promoters and enhancers reveal how specific LINE families have helped shape the dynamic mammalian regulome.
Sympathetic Nervous System and Exercise Affects Cognition in Youth (SNEACY): study protocol for a randomized crossover trial
Authors: Raine Lauren B. , McDonald Katherine , Shigeta Tatsuya T. , Hsieh Shu-Shih , Hunt Jennifer , Chiarlitti Nathan A. , Lim Michelle , Gebhardt Kristen , Collins Nina , De Lisio Michael , Mullen Sean P. , Kramer Arthur F. , Hillman Charles
Published: February 2021

Background

There is an increasing prevalence of physical inactivity during childhood, which is associated with a variety of health problems. However, the mechanisms by which acute exercise benefits cognition in childhood remains unknown. Here we describe the protocol for a randomized crossover trial called SNEACY (Sympathetic Nervous System & Exercise Affects Cognition in Youth), a study designed to better understand mechanisms linking acute exercise and cognition in 9–10-year-old healthy, cognitively normal children.

Methods

Children from the Greater Boston, MA region will be recruited to participate in this single center study. A randomized crossover design will be utilized, such that participants will act as their own controls, through initial randomization to condition assignment and condition counterbalancing across participants. One hundred three children will participate in three randomized acute interventions: moderate intensity treadmill exercise (20 min, 70–75% of their maximal heart rate), seated rest (20 min), and a Trier Social Stress Test for Children (14 min). These visits will occur on 3 three separate days, approximately 5–8 days apart. Before and after each intervention, children complete a variety of cognitive tasks measuring attentional inhibition while their neuroelectric activity is recorded. Variables of interest include EEG data, accuracy and reaction time, academic achievement, and salivary alpha amylase. Academic achievement is also assessed following interventions. In addition, children provide passive drool samples throughout the interventions to measure various biomarkers that may explain the acute exercise benefit on cognition.

Discussion

The results from this study could influence educational and public health recommendations to enhance cognition and learning in pre-adolescent children.

Trial registration

ClinicalTrials.gov NCT03592238. Registered on 19 July 2018
Utility of Abdominal Drain in Gastrectomy (ADiGe) Trial: study protocol for a multicenter non-inferiority randomized trial
Authors:   on behalf of the Italian Research Group for Gastric Cancer (GIRCG), Weindelmayer J. , Mengardo V. , Veltri A. , Baiocchi G. L. , Giacopuzzi S. , Verlato G. , de Manzoni G.
Published: February 2021

Background

Prophylactic use of abdominal drain in gastrectomy has been questioned in the last 15 years, and a 2015 Cochrane meta-analysis on four RCTs concluded that there was no convincing evidence to the routine drain placement in gastrectomy. Nevertheless, the authors evidenced the moderate/low quality of the included studies and highlighted how 3 out of 4 came from Eastern countries. After 2015, only retrospective studies have been published, all with inconsistent results.

Methods

ADiGe (Abdominal Drain in Gastrectomy) Trial is a multicenter prospective randomized non-inferiority trial with a parallel design. It aimed to verify whether avoiding routine use of abdominal drain is burdened with complications, particularly an increase in postoperative invasive procedures. Patients with gastric cancer, scheduled for subtotal or total gastrectomy with curative intent, are eligible for inclusion, irrespective of previous oncological treatment.

The primary composite endpoint is reoperation or percutaneous drainage procedures within 30 postoperative days. The primary analysis will verify whether the incidence of the primary composite endpoint is higher in the experimental arm, avoiding routine drain placement, than control arm, undergoing prophylactic drain placement, in order to falsify or support the null hypothesis of inferiority. Secondary endpoints assessed for superiority are overall morbidity and mortality, Comprehensive Complications Index, incidence and time for diagnosis of anastomotic and duodenal leaks, length of hospital stay, and readmission rate.

Assuming one-sided alpha of 5%, and cumulative incidence of the primary composite endpoint of 6.4% in the control arm and 4.2% in the experimental one, 364 patients allow to achieve 80% power to detect a non-inferiority margin difference between the arm proportions of 3.6%. Considering a 10% drop-out rate, 404 patients are needed. In order to have a balanced percentage between total and subtotal gastrectomy, recruitment will end at 202 patients for each type of gastrectomy. The surgeon and the patient are blinded until the end of the operation, while postoperative course is not blinded to the patient and caregivers.

Discussion

ADiGe Trial could contribute to critically re-evaluate the role of prophylactic drain in gastrectomy, a still widely used procedure.

Trial registration

Prospectively registered (last updated on 29 October 2020) at ClinicalTrials.gov with the identifier NCT04227951.
Sheep nemabiome diversity and its response to anthelmintic treatment in Swedish sheep herds
Authors: Halvarsson Peter , Höglund Johan
Published: February 2021

Background

A novel way to study the species composition and diversity of nematode parasites in livestock is to perform deep sequencing on composite samples containing a mixture of different species. Herein we describe for the first time the nematode community structures (nemabiomes) inhabiting Swedish sheep and how these are/were affected by host age and recent anthelmintic treatments.

Methods

A total of 158 fecal samples were collected (n = 35 in 2007 and n = 123 in 2013–2016) and cultured from groups of sheep on 61 commercial farms in the south-central part of the country where most animals are grazed. Among the samples, 2 × 44 (56%) were paired collections from the same groups pre- and post-treatment with anthelmintics such as macrocyclic lactones, benzimidazoles or levamisole. Samples were analyzed for their nemabiome using the PacBio platform followed by bioinformatic sequence analysis with SCATA. Species richness and diversity were calculated and analyzed in R.

Results

Nematode ITS2 sequences were found in all larval culture samples except two, even though the fecal egg counts were below the McMaster threshold in 20 samples. Sequencing yielded, on average, 1008 sequences per sample. In total, 16 operational taxonomical units (OTU), all with ≥ 98 % identity to sequences in the NCBI database, were recognized. The OTUs found represented nematode species of which ten are commonly associated with sheep. Multiple species were identified in all pre-anthelmintic treatment larval culture samples. No effects on nematode diversity were found in relation to host age. On the other hand, recent anthelmintic treatment lowered species richness, especially after use of ivermectin and albendazole. Interestingly, despite zero egg counts after use of levamisole, these samples still contained nematode DNA and especially H. contortus.

Conclusions

Our findings provide evidence that nemabiome analysis combined with diversity index analysis provides an objective methodology in the study of the efficacy of anthelmintic treatment as both high and low abundant species were detected.

Graphical Abstract
Curcumin and its analog alleviate diabetes-induced damages by regulating inflammation and oxidative stress in brain of diabetic rats
Authors: Miao Chengfeng , Chen Hanbin , Li Yulian , Guo Ying , Xu Feifei , Chen Qi , Zhang Yanyan , Hu Mengjun , Chen Guorong
Published: February 2021

Background

Diabetic encephalopathy is a severe diabetes complication with cognitive dysfunction and neuropsychiatric disability. The mechanisms underlying diabetic encephalopathy is believed to be relevant with oxidative stress, vascular amylin deposition, immune receptors, inflammation, etc. This study wanted to evaluate the ability of curcumin and its analog A13 to alleviate oxidative stress and inflammation in diabetes-induced damages in brain.

Methods

Sixty adult male Sprague–Dawley rats were divided into 5 groups: normal control (NC) group, diabetes mellitus (DM) group, curcumin-treated diabetes mellitus (CUR) group, high dose of A13-treated diabetes mellitus (HA) group, low dose of A13-treated diabetes mellitus (LA) group. Activation of the nuclear factor kappa-B (NF-κB p65) pathway was detected by RT-qPCR, immunohistochemical (IHC) staining and Western blot; oxidative stress was detected by biochemical detection kit; brain tissue sections were stained with hematoxylin–eosin (HE) staining and Myelin staining.

Results

RT-qPCR, IHC staining and Western blot showed that curcumin and A13 treatment could inhibit the NF-κB p65 pathway. Curcumin and A13 increased the activity of superoxide dismutase and decreased the malondialdehyde level in the brain of diabetic rats. Furthermore, HE staining and Myelin staining demonstrated that the histological lesions of the brain in diabetic rats could be significantly ameliorated by curcumin and A13.

Conclusion

Curcumin analog A13 could alleviate the damages in the brain of diabetes rats by regulating the pathways of inflammation and oxidative stress. A13 may be a new potential therapeutic agent for diabetic encephalopathy.
The application of next-generation sequence-based DNA barcoding for bloodmeal detection in host-seeking wild-caught Ixodes scapularis nymphs
Authors: Lumsden G. A. , Zakharov E. V. , Dolynskyj S. , Weese J. S. , Lindsay L. R. , Jardine C. M.
Published: February 2021

Objective

Our objective was to apply next-generation sequence-based DNA barcoding to identify the remnant larval bloodmeals in wild-caught host-seeking (unengorged)Ixodes scapularisnymphs (n = 216). To infer host species identification, vertebrate DNA was amplified using universal primers for cytochromecoxidase subunit I (COI) and sequenced using next-generation sequencing (NGS) for comparison against known barcode references.

Results

Bloodmeal identification was unsuccessful in most samples (99% of 216 specimens) demonstrating a very low detection rate of this assay. Sequences that surpassed quality thresholds were obtained for 41.7% of nymphs (n = 90) and of those, confident species identification was obtained for 15.6% of nymphs (n = 14). Wild host identifications were only obtained from 2 specimens, where DNA from the eastern grey squirrel (Sciurus carolinensis) was identified. Human and bovine DNA was identified in remaining nymphs and considered to be contaminants. Further optimization of the technique is required to improve detection of remnant bloodmeals in host-seeking nymphs.