bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of serum choline levels and all-cause mortality risk in adults with hypertension: a nested case–control study
Authors: Song Mengmeng , Xu Benjamin P. , Liang Qiongyue , Wei Yaping , Song Yun , Chen Ping , Zhou Ziyi , Zhang Nan , He Qiangqiang , Liu Lishun , Liu Tong , Zhang Kangping , Hu Chunlei , Wang Binyan , Xu Xiping , Shi Hanping
Published: December 2021

Background

Serum choline levels were associated with multiple chronic diseases. However, the association between serum choline and all-cause mortality in Chinese adults with hypertension remains unclear. The purpose of this study is to explore the association between serum choline concentrations and all-cause mortality risk in Chinese adults with hypertension, a high-risk population.

Methods

A nested, case–control study was conducted that included 279 patients with all-cause death, and 279 matched, living controls, derived from the China Stroke Primary Prevention Trial (CSPPT). Baseline serum choline concentrations were measured by liquid chromatography with tandem quadrupole mass spectrometry (LC–MS/MS). Multivariate logistic regression analysis was used to assess the association of serum choline levels and all-cause mortality risk, with adjustment of pertinent covariables, including folic acid and homocysteine.

Results

The median age of all participants was 64.13 years [interquartile range (IQR), 57.33–70.59 years]. The median serum choline concentration for cases (9.51 μg/mL) was higher than that in controls (7.80 μg/mL) (P = 0.009). When serum choline concentration was assessed as a continuous variable (per SD increased), there was a positive relation between serum choline levels and all-cause mortality risk [odds ratios (OR), 1.29; 95% confidence intervals (95%CI), 1.06–1.57; P = 0.010]. There was an increased all-cause mortality risk for participants in quartiles 2–4 (≥ 4.00 μg/mL; OR, 1.79; 95%CI, 1.15–2.78 compared with quartile 1 (< 4.00 μg/mL). In addition, non-drinking was found to promote the incidence of all-cause mortality for those with high choline concentrations.

Conclusions

High serum choline concentrations were associated with increased all-cause mortality risk among Chinese adults with hypertension, compared to lower choline concentrations.

Trial registration clinicaltrials.gov Identifier: NCT007948885; UTL: https://clinicaltrials.gov/ct2/show/NCT00794885?term=NCT00794885&draw=2&rank=1.
Three weekly versus weekly concurrent cisplatin: safety propensity score analysis on 166 head and neck cancer patients
Authors: Buglione Michela , Alterio Daniela , Maddalo Marta , Greco Diana , Gerardi Marianna Alessandra , Tomasini Davide , Pegurri Ludovica , Augugliaro Matteo , Marvaso Giulia , Turturici Irene , Guerini Andrea , Ansarin Mohssen , Spiazzi Luigi , Costa Loredana , Cossu Rocca Maria , Magrini Stefano Maria , Jereczek-Fossa Barbara Alicja
Published: December 2021

Background

Radio-chemotherapy with CDDP is the standard for H&N squamous cell cancer. CDDP 100 mg/m2/q3 is the standard; alternative schedules are used to reduce toxicity, mostly 40 mg/m2/q1.

Methods

Patients were treated from 1/2010 to 1/2017 in two Radiation Oncology Centres. Propensity score analysis (PS) was retrospectively used to compare these two schedules.

Results

Patients analyzed were 166. Most (114/166) had 1w-CDDP while 52 had 3w-CDDP. In the 3w-CDDP group, patients were younger, with better performance status, smaller disease extent and a more common nodal involvement than in the 1w-CDDP. Acute toxicity was similar in the groups. Treatment compliance was lower in the w-CCDP. Overall survival before PS was better for female, for oropharyngeal disease and for 3w-CDDP group. After PS, survival was not related to the CDDP schedule.

Conclusions

3w-CDDP remains the standard for fit patients, weekly schedule could be safely used in selected patients.
Down-regulation of circ_0058058 suppresses proliferation, angiogenesis and metastasis in multiple myeloma through miR-338-3p/ATG14 pathway
Authors: Xue Lianguo , Jia Tao , Zhu Yuanxin , Zhao Lidong , Mao Jianping
Published: December 2021

Background

Multiple myeloma (MM) is one of the most frequently diagnosed hematological malignancy. Dysregulation of circular RNAs (circRNAs) has important impacts on MM process. Herein, this work aimed to investigate the role and mechanism of circ_0058058 in MM progression.

Methods

Levels of genes and proteins were detected by real-time reverse transcription PCR (RT-qPCR) and Western blot. CCK-8 assay, colony formation assay, EdU assay, flow cytometry, tube formation assay, transwell assay and Western blot were utilized to detect the proliferation, apoptosis, angiogenesis and metastasis of MM cells. The target relationship between miR-338-3p and circ_0058058 or ATG14 (autophagy related 14) was verified by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. In vivo experiments were performed using Xenograft assay.

Results

Circ_0058058 was up-regulated in MM bone marrow aspirates and cells, knockdown of circ_0058058 reduced MM cell proliferation, angiogenesis and metastasis, but induced apoptosis in vitro. In a MM xenograft mouse model, circ_0058058 silencing reduced MM tumor growth and cell proliferation. Mechanistically, circ_0058058 acted as a sponge for miR-338-3p to up-regulate ATG14 expression, which was validated to be a target of miR-338-3p. Rescue assay showed that miR-338-3p inhibition reversed the antitumor effects of circ_0058058 knockdown on MM cell. Moreover, forced expression of miR-338-3p suppressed MM cell malignant phenotype, which was abolished by ATG14 up-regulation.

Conclusion

Circ_0058058 functions as a sponge for miR-338-3p to elevate ATG14 expression to promote MM cell proliferation, metastasis and angiogenesis, affording a potential therapeutic target for MM prevention.
Pathways to mental health care in Nepal: a 14-center nationwide study
Authors: Gupta Anoop Krishna , Joshi Sulochana , Kafle Bikram , Thapa Ranjan , Chapagai Manisha , Nepal Suraj , Niraula Abhash , Paudyal Sreya , Sapkota Prabhat , Poudel Reet , Gurung Bina Sing , Pokhrel Prabhakar , Jha Robin , Pandit Sanjib , Thapaliya Suresh , Shrestha Shuva , Volpe Umberto , Sartorius Norman
Published: December 2021

Background

Pathways to care studies are feasible and tested means of finding the actual routes taken by patients before reaching proper care. In view of the predominance of nonprofessional service providers and the lack of previous large studies on pathways in Nepal, this multicenter study is needed. The aim of the study was to trace the various pathways and carers involved in mental health care; assess clinical variables such as the duration of untreated illness, clinical presentation and treatment; and compare geographically and culturally diverse landscapes.

Methods

This was a cross-sectional, convenience sampling study performed at 14 centers where new cases were being taken. The World Health Organization Study of the Pathways-to-Care Schedule was applied. The Nepali version of the encounter form was used. The data were collected between 17 September and 16 October 2020 and were analyzed using the Statistical Package for the Social Sciences (SPSS). Additionally, perspectives from local investigators were collected and discussed.

Results

Most of the first carers were native/religious faith healers (28.2%), followed by psychiatrists (26%). The median duration for the first psychiatric consultation was 3 weeks. The duration of untreated illness was 30.72 ± 80.34 (median: 4) weeks, and the time taken for this journey was 94.99 ± 274.58 (median: 30) min. The longest delay from the onset of illness to psychiatric care was for epilepsy {90.0 ± 199.0 (median: 25.5)} weeks, followed by neurotic illness {22.89 ± 73.45 (median: 2)} and psychotic illness {10.54 ± 18.28 (median: 2)} weeks. Overall, most patients with severe mental illnesses (SMIs) had their first contact with faithhealers (49%), then met with medical doctors (13%) or psychiatrists (28%). Marked differences in clinical presentation surfaced when hilly centers were compared with the Terai belt.

Conclusions

Faith healers, general practitioners and hospital doctors are major carers, and the means of educating them for proper referral can be considered. The investigators see several hindrances and opportunities in the studied pathways. The employment of more mental health professionals and better mental health advocacy, public awareness programs and school education are suggested strategies to improve proper mental health care.
Retraction Note: TGF-β2 initiates autophagy via Smad and non-Smad pathway to promote glioma cells’ invasion
Authors: Zhang Chao , Zhang Xin , Xu Ran , Huang Bin , Chen An-Jing , Li Chao , Wang Jian , Li Xin-Gang
Published: December 2021

This article has been retracted. Please see the Retraction Notice for more detail: https://doi.org/10.1186/s13046-021-02219-8.
OPHTHALMIA NEONATORUM in Italy: it is time for change
Authors: Auriti Cinzia , Mondì Vito , Aversa Salvatore , Merazzi Daniele , Lozzi Simona , Petroni Sergio , Baldascino Antonio , Massenzi Luca , Bellù Roberto , Martinelli Stefano , Mosca Fabio
Published: December 2021

Ophthalmia neonatorum (ON) refers to any conjunctivitis occurring in the first 28 days of life. In the past Neisseria gonorrhoeae was the most common cause of ON. It decreased with the introduction of prophylaxis at birth with the instillation of silver nitrate 2% (the Credè’s method of prophylaxis). Today, the term ON is used to define any other bacterial infection, in particular due to Chlamydia Trachomatis. Currently, the WHO reccomends topical ocular prophylaxis for prevention of gonococcal and chlamydial conjunctivitis for all neonates. On the contrary, several European countries no longer require universal prophylaxis, opting for screening and treatment of pregnant women at high risk of infection. And what about Italy? Have a look on Italian history of prophylaxis, starting by the first decree issued in 1940, signed by Benito Mussolini. In the following decades the law has undergone many changes. At the moment, legislation is unclear, therefore careful consideration is required in order to draft the correct appoach.
HIV-1LAI Nef blocks the development of hematopoietic stem/progenitor cells into myeloid-erythroid lineage cells
Authors: Zou Wei , Xing Juanjuan , Zou Shijie , Jiang Mei , Chen Xinping , Chen Qi , Liu Daozheng , Zhang Xiangcheng , Fu Xin
Published: December 2021

Background

A variety of hematopoietic abnormalities are commonly seen in human immunodeficiency virus-1 (HIV-1) infected individuals despite antiviral therapy, but the underlying mechanism remains elusive. Nef plays an important role in HIV-1 induced T cell loss and disease progression, but it is not known whether Nef participates in other hematopoietic abnormalities associated with infection.

Results

In the current study we investigated the influence of HIV-1LAI Nef (LAI Nef) on the development of hematopoietic stem/progenitor cells (HSPCs) into myeloid-erythroid lineage cells, and found that nef expression in HSPCs blocked their differentiation both in vitro and in humanized mice reconstituted with nef-expressing HSPCs.

Conclusions

Our novel findings demonstrate LAI Nef compromised the development of myeloid-erythroid lineage cells, and therapeutics targeting Nef would be promising in correcting HIV-1 associated hematopoietic abnormalities.
Augmenting an online self-directed intervention for gambling disorder with a single motivational interview: study protocol for a randomized controlled trial
Authors: Brazeau Brad W. , Hodgins David C. , Cunningham John A. , Bennett Kylie , Bennett Anthony
Published: December 2021

Background

Despite the success of gold standard cognitive-behavioral therapy for problem and disordered gambling, the majority of individuals with gambling problems do not seek or receive professional treatment. Thus, the development of less intrusive self-directed interventions has been encouraged. Bibliotherapy for problem gambling has shown promise, both alone and in combination with motivational interviews, but there is still a lack of online self-directed intervention research. The current randomized controlled trial proposes to assess the additive benefit of a single digital motivational interview delivered in conjunction with an online self-directed treatment program for problem gambling and gambling disorder.

Methods

A two-arm randomized controlled trial will be conducted, wherein eligible participants (N=270) will be recruited across Canada via internet advertisements posted to several platforms. All participants will receive access to an online self-directed gambling intervention program. Participants will be randomly assigned to either complete the online program alone or receive a digital motivational interview, conducted through an online audioconferencing platform (i.e., Microsoft Teams) to supplement the online program. The primary outcomes of gambling severity, frequency, and expenditures will be tracked along with secondary outcomes (i.e., depression, anxiety, general distress, alcohol use, and online program user data) over a 24-month period. It is expected that participants in both groups will experience a reduction in symptoms across the board, but more substantial improvements will be observed in the group that receives a supplemental motivational interview.

Discussion

The results of this trial will expand upon prior gambling intervention research by informing best practices for the provision of online self-help for problem gambling.

Trial registration

ISRCTN ISRCTN13009468. Registered on 7 July 2020.
The ecdysteroid receptor regulates salivary gland degeneration through apoptosis in Rhipicephalus haemaphysaloides
Authors: Lu Xiaojuan , Zhang Zhipeng , Yuan Dongqi , Zhou Yongzhi , Cao Jie , Zhang Houshuang , da Silva Vaz Itabajara , Zhou Jinlin
Published: December 2021

Background

It is well established that ecdysteroid hormones play an important role in arthropod development and reproduction, mediated by ecdysteroid receptors. Ticks are obligate hematophagous arthropods and vectors of pathogens. The salivary gland plays an essential role in tick growth and reproduction and in the transmission of pathogens to vertebrate hosts. During tick development, the salivary gland undergoes degeneration triggered by ecdysteroid hormones and activated by apoptosis. However, it is unknown how the ecdysteroid receptor and apoptosis regulate salivary gland degeneration. Here, we report the functional ecdysteroid receptor (a heterodimer of the ecdysone receptor [EcR] and ultraspiracle [USP]) isolated from the salivary gland of the tick Rhipicephalus haemaphysaloides and explore the molecular mechanism of ecdysteroid receptor regulation of salivary gland degeneration.

Methods

The full length of RhEcR and RhUSP open reading frames (ORFs) was obtained from the transcriptome. The RhEcR and RhUSP proteins were expressed in a bacterial heterologous system, Escherichia coli. Polyclonal antibodies were produced against synthetic peptides and were able to recognize recombinant and native proteins. Quantitative real-time PCR and western blot were used to detect the distribution of RhEcR, RhUSP, and RhCaspases in the R. haemaphysaloides organs. A proteomics approach was used to analyze the expression profiles of the ecdysteroid receptors, RhCaspases, and other proteins. To analyze the function of the ecdysteroid receptor, RNA interference (RNAi) was used to silence the genes in adult female ticks. Finally, the interaction of RhEcR and RhUSP was identified by heterologous co-expression assays in HEK293T cells.

Results

We identified the functional ecdysone receptor (RhEcR/RhUSP) of 20-hydroxyecdysone from the salivary gland of the tick R. haemaphysaloides. The RhEcR and RhUSP genes have three and two isoforms, respectively, and belong to a nuclear receptor family but with variable N-terminal A/B domains. The RhEcR gene silencing inhibited blood-feeding, blocked engorgement, and restrained salivary gland degeneration, showing the biological role of the RhEcR gene in ticks. In the ecdysteroid signaling pathway, RhEcR silencing inhibited salivary gland degeneration by suppressing caspase-dependent apoptosis. The heterologous expression in mammalian HEK293T cells showed that RhEcR1 interacts with RhUSP1 and induces caspase-dependent apoptosis.

Conclusions

These data show that RhEcR has an essential role in tick physiology and represents a putative target for the control of ticks and tick-borne diseases.

Graphical Abstract
In vitro characterization of Haemonchus contortus trehalose-6-phosphate phosphatase and its immunomodulatory effects on peripheral blood mononuclear cells (PBMCs)
Authors: Wen ZhaoHai , Xie XinRan , Aleem Muhammad Tahir , Aimulajiang Kalibixiati , Chen Cheng , Liang Meng , Song XiaoKai , Xu LiXin , Li XiangRui , Yan RuoFeng
Published: December 2021

Background

Trehalose-6-phosphate phosphatase (TPP6) is a key enzyme in the trehalose biosynthesis pathway. The accumulation of TPP6 inside the body is harmful to the pathogen, but almost nothing is currently known about the function of TPP6 from Haemonchus contortus (CRE-GOB-1).

Methods

The H. contortus CRE-GOB-1 (HcGOB) gene was cloned and recombinant protein of GOB (rHcGOB) was expressed; transcription of the HcGOB gene at different developmental stages of H. contortus was then studied. The spatial expression pattern of the HcGOB gene in adult female and male worms was determined by both quantitative real-time PCR (qPCR) and immunofluorescence. The binding of the rHcGOB protein to goat PBMCs was assessed by immunofluorescence assay. The immunomodulatory impacts of rHcGOB on cell proliferation, nitric oxide generation and cytokine secretion were assessed by co-culture of rHcGOB protein with goat PBMCs.

Results

The HcGOB protein was transcribed in eggs, infective third-stage larvae (iL3s) and adults of H. contortus, with the highest transcript levels found in the egg stage. The transcript levels were significantly elevated in iL3s after manual desheathing. HcGOB was widely distributed in adult worms where it was mainly localized in the gut and gonads. rHcGOB was observed to bind to PBMCs and also to be recognized by sera collected from a goat infected with H. contortus. rHcGOB significantly activated the interleukin-10/transforming growth factor β/signal transducer and activator of transcription 3 (IL-10/TGF-β/STAT3) pathway in PBMCs while suppressing the transcription and expression of IL-4 and IL-17.

Conclusions

These results suggest that the HcGOB gene plays an important role in the development, parasitism and reproduction of H. contortus. The rHcGOB protein affected the immunomodulatory function of PBMCs in the in vitro study, suggesting that this protein would be a promising vaccine target.

Graphical Abstract
Can adults with cerebral palsy perform and benefit from ballistic strength training to improve walking outcomes? A mixed methods feasibility study
Authors: Gjesdal Beate Eltarvåg , Mæland Silje , Williams Gavin , Aaslund Mona Kristin , Rygh Cecilie Brekke , Cumming Kristoffer Toldnes
Published: December 2021

Background

Power bursts of hips and ankle plantar flexors are prerequisites to walking propulsion. However, these power bursts are reduced during gait for persons with cerebral palsy (CP) and mainly in the ankle plantar flexors. Hence, task specific training, such as ballistic strength training, is suggested to increase muscle power in walking but not investigated in adults with CP. Therefore, the aim was to investigate if adults with CP could perform and benefit from ballistic strength training to improve walking, evaluated through physical measures and self-reported measures and interviews.

Methods

In this mixed methods feasibility study, eight ambulatory adults (aged 24–56) with spastic CP conducted ballistic strength training on a glideboard targeting the ankle plantarflexors two times a week for eight weeks. The feasibility of the training was assessed through objectives described by Orsmond and Cohn. Before and after the intervention, physical measures (6-Minute Walk Test and the eight-item High-level Mobility Assessment Tool) and self-reported measures (Patient Global Impression of Change, Numeric Pain Rating Scale, Fatigue Impact and Severity Self-Assessment, and Walk-12) were collected. After the intervention, semi-structured interviews explored experiences of this training.

Results

The participants experienced training the ankle plantar flexor as relevant but reported it took about four weeks to coordinate the exercises successfully. Although we observed no changes in the physical performance measures, most participants reported improvements; some felt steadier when standing, walking, and hopping.

Conclusion

This study demonstrated that ballistic strength training was feasible and suitable in adults with CP. However, guidance and a long (4 weeks) familiarization time were reported necessary to master the exercises. Most participants reported self-experienced improvements, although no physical performance measures improved. Thus, prolonged intervention may be required for perceived physical improvements to emerge. Also, other outcome measures sensitive to power output remains to be investigated.
Lessons learned during implementation of MR-guided High-Intensity Focused Ultrasound treatment of uterine fibroids
Authors: Anneveldt K. J. , Verpalen I. M. , Nijholt I. M. , Dijkstra J. R. , van den Hoed R. D. , van’t Veer-ten Kate M. , de Boer E. , van Osch J. A. C. , Heijman E. , Naber H. R. , Ista E. , Franx A. , Veersema S. , Huirne J. A. F. , Schutte J. M. , Boomsma M. F.
Published: December 2021

Background

Although promising results have been reported for Magnetic Resonance image-guided High-Intensity Focused Ultrasound (MR-HIFU) treatment of uterine fibroids, this treatment is not yet widely implemented in clinical practice. During the implementation of a new technology, lessons are learned and an institutional learning-curve often has to be completed. The primary aim of our prospective cohort study was to characterize our learning-curve based on our clinical outcomes. Secondary aims included identifying our lessons learned during implementation of MR-HIFU on a technical, patient selection, patient counseling, medical specialists and organizational level.

Results

Our first seventy patients showed significant symptom reduction and improvement of quality of life at 3, 6 and 12 months after MR-HIFU treatment compared to baseline. After the first 25 cases, a clear plateau phase was reached in terms of failed treatments. The median non-perfused volume percentage of these first 25 treatments was 44.6% (range: 0–99.7), compared to a median of 74.7% (range: 0–120.6) for the subsequent treatments.

Conclusions

Our findings describe the learning-curve during the implementation of MR-HIFU and include straightforward suggestions to shorten learning-curves for future users. Moreover, the lessons we learned on technique, patient selection, patient counseling, medical specialists and organization, together with the provided supplements, may be of benefit to other institutions aiming to implement MR-HIFU treatment of uterine fibroids.

Trial registration ISRCTN14634593. Registered January 12, 2021—Retrospectively registered, https://www.isrctn.com/ISRCTN14634593.
Risk of metastatic disease using [18F]PSMA-1007 PET/CT for primary prostate cancer staging
Authors: Chikatamarla Venkata Avinash , Okano Satomi , Jenvey Peter , Ansaldo Alexander , Roberts Matthew J. , Ramsay Stuart C. , Thomas Paul A. , Pattison David A.
Published: December 2021

Background

Accurate prostate cancer imaging is critical for patient management. Multiple studies have demonstrated superior diagnostic accuracy of [68Ga]-PSMA-11 PET/CT over conventional imaging for disease detection, with validated clinical and biochemical predictors of disease detection. More recently [18F]PSMA-1007 offers theoretical imaging advantages, but there is limited evidence of clinical and biochemical predictors of scan findings in the staging population. This study investigates the association of clinical variables with imaging characteristics among patients who underwent [18F]PSMA-1007 PET/CT for primary staging of men with histopathologically confirmed prostate carcinoma. A retrospective review of 194 consecutive patients imaged between May 2019 to May 2020 was performed. Association between imaging variables (presence and distribution of metastatic disease, primary tumour SUVmax) and clinical variables (EAU risk criteria) were assessed using descriptive statistics, logistic regression model and ROC analysis.

Results

The median age, PSA level and ISUP grade were 70 years, 10 ng/mL and ISUP grade 3, respectively. There were 36.6% of patients with intermediate-risk and 60.8% of patients with high-risk disease. ISUP grade was associated with the presence of metastasis overall (p = 0.008) as well as regional nodal (p = 0.003), non-regional nodal (p = 0.041) and bone (p = 0.006) metastases. PSA level was associated with metastatic disease overall (p = 0.001), regional (p = 0.001) and non-regional nodal metastases (p = 0.004), but not with bone metastases (p = 0.087). There were too few visceral metastases for meaningful analysis. SUVmax of the primary prostatic tumour was associated with ISUP grade (p = 0.004), PSA level (p < 0.001) and AJCC stage (p = 0.034). PSA > 20 ng/mL and ISUP grade > 3 had a specificity of 85% (95% CI 78–91%) and 60% (95% CI 50–68%) and a sensitivity of 36% (95% CI 25–49%) and 62% (95% CI 49–74%), respectively, for detection of metastatic disease.

Conclusion

Metastatic disease according to [18F]PSMA-1007 PET/CT was associated with ISUP grade and PSA level. This is the largest study using [18F]PSMA-1007 PET/CT to confirm a positive correlation of PSA level, ISUP grade and stage with primary prostate tumour SUVmax.
Anchor voiceprint recognition in live streaming via RawNet-SA and gated recurrent unit
Authors: Yao Jiacheng , Zhang Jing , Li Jiafeng , Zhuo Li
Published: December 2021

With the sharp booming of online live streaming platforms, some anchors seek profits and accumulate popularity by mixing inappropriate content into live programs. After being blacklisted, these anchors even forged their identities to change the platform to continue live, causing great harm to the network environment. Therefore, we propose an anchor voiceprint recognition in live streaming via RawNet-SA and gated recurrent unit (GRU) for anchor identification of live platform. First, the speech of the anchor is extracted from the live streaming by using voice activation detection (VAD) and speech separation. Then, the feature sequence of anchor voiceprint is generated from the speech waveform with the self-attention network RawNet-SA. Finally, the feature sequence of anchor voiceprint is aggregated by GRU to transform into a deep voiceprint feature vector for anchor recognition. Experiments are conducted on the VoxCeleb, CN-Celeb, and MUSAN dataset, and the competitive results demonstrate that our method can effectively recognize the anchor voiceprint in video streaming.
Some aspects of nonsmooth variational inequalities on Hadamard manifolds
Authors: Islam Monirul , Irfan Syed Shakaib
Published: December 2021

This is the first paper dealing with the study of minimum and maximum principle sufficiency properties for nonsmooth variational inequalities by using gap functions in the setting of Hadamard manifolds. We also provide some characterizations of these two sufficiency properties. We conclude the paper with a discussion of the error bounds for nonsmooth variational inequalities in the setting of Hadamard manifolds.
A case of solitary plasmacytoma of bone showing co-expression of both immunoglobulin light chains
Authors: Matsuoka Ryota , Sakamoto Noriaki , Kato Takayasu , Chiba Shigeru , Noguchi Masayuki
Published: December 2021

Background

Solitary plasmacytoma of bone (SPB) is a rare plasma cell neoplasm. It arises in bone as a single locus in the absence of any plasma cell myeloma lesions. Plasma cell neoplasms intrinsically express only one immunoglobulin light chain (IgL)—kappa or lambda—and using this fact, kappa/lambda deviation is the decisive factor for diagnosis. Co-expression of both IgLs in a single tumor cell is extremely rare.

Case presentation

We report a case of SPB that arose in the vertebra of a 52-year-old Japanese woman. Histologically, the resected mass showed diffuse plasma cell proliferation. Dual IgL expression was detected by flow cytometry, immunohistochemistry, and in situ hybridization (ISH) targeting IgL mRNA.

Conclusion

We have presented an extremely rare case of SPB showing dual expression of kappa and lambda IgLs. This unusual case of plasma cell neoplasia might represent a possible exceptional example of failure of “IgL isotypic exclusion.”
Glutamic acid reshapes the plant microbiota to protect plants against pathogens
Authors: Kim Da-Ran , Jeon Chang-Wook , Cho Gyeongjun , Thomashow Linda S. , Weller David M. , Paik Man-Jeong , Lee Yong Bok , Kwak Youn-Sig
Published: December 2021

Background

Plants in nature interact with other species, among which are mutualistic microorganisms that affect plant health. The co-existence of microbial symbionts with the host contributes to host fitness in a natural context. In turn, the composition of the plant microbiota responds to the environment and the state of the host, raising the possibility that it can be engineered to benefit the plant. However, technology for engineering the structure of the plant microbiome is not yet available.

Results

The loss of diversity and reduction in population density ofStreptomyces globisporusSP6C4, a core microbe, was observed coincident with the aging of strawberry plants. Here, we show that glutamic acid reshapes the plant microbial community and enriches populations ofStreptomyces, a functional core microbe in the strawberry anthosphere. Similarly, in the tomato rhizosphere, treatment with glutamic acid increased the population sizes ofStreptomycesas well as those of Bacillaceae and Burkholderiaceae. At the same time, diseases caused by species ofBotrytisandFusariumwere significantly reduced in both habitats. We suggest that glutamic acid directly modulates the composition of the microbiome community.

Conclusions

Much is known about the structure of plant-associated microbial communities, but less is understood about how the community composition and complexity are controlled. Our results demonstrate that the intrinsic level of glutamic acid in planta is associated with the composition of the microbiota, which can be modulated by an external supply of a biostimulant.
Detection of low-level parental somatic mosaicism for clinically relevant SNVs and indels identified in a large exome sequencing dataset
Authors: Domogala Daniel D. , Gambin Tomasz , Zemet Roni , Wu Chung Wah , Schulze Katharina V. , Yang Yaping , Wilson Theresa A. , Machol Ido , Liu Pengfei , Stankiewicz Paweł
Published: December 2021

Background

Due to the limitations of the current routine diagnostic methods, low-level somatic mosaicism with variant allele fraction (VAF) < 10% is often undetected in clinical settings. To date, only a few studies have attempted to analyze tissue distribution of low-level parental mosaicism in a large clinical exome sequencing (ES) cohort.

Methods

Using a customized bioinformatics pipeline, we analyzed apparent de novo single-nucleotide variants or indels identified in the affected probands in ES trio data at Baylor Genetics clinical laboratories. Clinically relevant variants with VAFs between 30 and 70% in probands and lower than 10% in one parent were studied. DNA samples extracted from saliva, buccal cells, redrawn peripheral blood, urine, hair follicles, and nail, representing all three germ layers, were tested using PCR amplicon next-generation sequencing (amplicon NGS) and droplet digital PCR (ddPCR).

Results

In a cohort of 592 clinical ES trios, we found 61 trios, each with one parent suspected of low-level mosaicism. In 21 parents, the variants were validated using amplicon NGS and seven of them by ddPCR in peripheral blood DNA samples. The parental VAFs in blood samples varied between 0.08 and 9%. The distribution of VAFs in additional tissues ranged from 0.03% in hair follicles to 9% in re-drawn peripheral blood.

Conclusions

Our study illustrates the importance of analyzing ES data using sensitive computational and molecular methods for low-level parental somatic mosaicism for clinically relevant variants previously diagnosed in routine clinical diagnostics as apparent de novo.
A three-wave longitudinal study on the relation between commuting strain and somatic symptoms in university students: exploring the role of learning-family conflicts
Authors: Diebig Mathias , Li Jian , Forthmann Boris , Schmidtke Jan , Muth Thomas , Angerer Peter
Published: December 2021

Background

We examine the role of learning-family conflicts for the relation between commuting strain and health in a sample of medical university students. The first goal of the study was to investigate the mediating role of learning-family conflicts. The second goal was to extend the temporal view on relations between study variables. Therefore, we differentiated long-term systematic change among variables over a period of two-years from a dynamic perspective with repeated commuting events on the individual level of analyses.

Methods

We applied a multilevel research design and collected survey data from 128 medical students on three points in time (N = 339 measurement points). Participants informed about commuting strain, learning-family conflicts, somatic symptoms, as well as commuting distance and time.

Results

Bayesian multilevel analyses showed that results differed with regard to level of analysis: while learning-family conflicts mediated the relation between commuting strain and somatic symptoms on a systematic aggregation-level perspective of analysis (indirect effect estimatebetween = 0.13, SE = .05, 95% CI [0.05; ∞), Evidence Ratio = 250.57), this was not the case on the dynamic event perspective (indirect effect estimatewithin = 0.00, SE = 0.00, 95% CI [− 0.01; ∞), Evidence Ratio = 0.84).

Conclusions

We demonstrated that learning-family conflicts explain why commuting may have unfavorable effects on health for medical students. We also showed that it is the long-term commuting experience that is related to health complaints and not the single commuting event. This means that short-term deviations from general levels of commuting strain do not cause somatic symptoms, but general high levels of commuting strain do instead.
Inside the biology of early T-cell precursor acute lymphoblastic leukemia: the perfect trick
Authors: Tarantini Francesco , Cumbo Cosimo , Anelli Luisa , Zagaria Antonella , Specchia Giorgina , Musto Pellegrino , Albano Francesco
Published: December 2021

Early T-cell precursor acute lymphoblastic leukemia (ETP-ALL) is a rare, distinct subtype of T-ALL characterized by genomic instability, a dismal prognosis and refractoriness to standard chemotherapy. Since its first description in 2009, the expanding knowledge of its intricate biology has led to the definition of a stem cell leukemia with a combined lymphoid-myeloid potential: the perfect trick. Several studies in the last decade aimed to better characterize this new disease, but it was recognized as a distinct entity only in 2016. We review current insights into the biology of ETP-ALL and discuss the pathogenesis, genomic features and their impact on the clinical course in the precision medicine era today.
Role of clinical pharmacists in epilepsy management at a general hospital in Vietnam: a before-and-after study
Authors: Pham Hong Tham , Tran Minh-Hoang , Nguyen Ngoc Quy , Tan Vo Van , Tran Manh Hung
Published: December 2021

Background

Clinical pharmacists have an important role in inter-professional healthcare collaboration for epilepsy management. However, the pharmacy practices of managing epilepsy are still limited in Vietnam, deterring pharmacists from routine adjustments of antiepileptic drugs, which could decrease the patients’ quality of life. This study aimed to assess the effectiveness of pharmacist interventions in epilepsy treatment at a Vietnamese general hospital.

Methods

A before-and-after study was conducted from January 2016 to December 2018. All patients with a diagnosis of epilepsy and being treated at the investigated hospital were recruited and screened for eligibility and exclusion criteria. The primary outcome was the proportion of patients in good control of their epilepsy (with two seizures or less in a year). The secondary outcome was the number of patients maintaining optimized concentrations within the therapeutic range of carbamazepine (4–12 mg/L), phenytoin (10–20 mg/L), or valproic acid (50–100 mg/L). Collected data were analyzed using two proportions Z-test or Chi-square test.

Results

A total of 141 participants were enrolled in the study. While most patients were given lower prescribed daily doses than the recommendations from the World Health Organization, over 56% of the participants still experienced adverse drug effects. More than half of the patients received at least one pharmacists’ intervention, which increased by 25.0% the effectiveness of the therapy (p < 0.001) and by 14.6% the number of patients with optimized drug concentrations (p = 0.018).

Conclusion

Epilepsy management requires a multiple-stepped and comprehensive approach, with a focus on the health and safety of the patients. As part of the healthcare team, pharmacists need to engage at every stage to monitor the patient’s response and determine the most effective treatment with the fewest adverse drug reactions.

Trial registration ClinicalTrials.gov, NCT04967326. Registered July 19, 2021—Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04967326
Extreme IOD induced tropical Indian Ocean warming in 2020
Authors: Zhang Ying , Du Yan
Published: December 2021

The tropical Indian Ocean (TIO) basin-wide warming occurred in 2020, following an extreme positive Indian Ocean Dipole (IOD) event instead of an El Niño event, which is the first record since the 1960s. The extreme 2019 IOD induced the oceanic downwelling Rossby waves and thermocline warming in the southwest TIO, leading to sea surface warming via thermocline-SST feedback during late 2019 to early 2020. The southwest TIO warming triggered equatorially antisymmetric SST, precipitation, and surface wind patterns from spring to early summer. Subsequently, the cross-equatorial “C-shaped” wind anomaly, with northeasterly–northwesterly wind anomaly north–south of the equator, led to basin-wide warming through wind-evaporation-SST feedback in summer. This study reveals the important role of air–sea coupling processes associated with the independent and extreme IOD in the TIO basin-warming mode, which allows us to rethink the dynamic connections between the Indo-Pacific climate modes.
Community-based medication disposal pilot initiative in southwest tribal communities
Authors: Ampadu Isaac , Morones Robert , Tsatoke Andrea , Ampadu Lacie , Stephens Martin , Crump William C. , Bales David
Published: December 2021

Background

Misuse and abuse of prescription drugs including opioids has been a driving force behind the drug overdose epidemic plaguing communities across the USA for more than two decades. Medication accumulation in the home environment can contribute to this issue. However, research on proper disposal in rural communities is limited. For this project, an applied public health approach was used to raise awareness and improve prescription drug disposal practices by pilot testing prescription drug disposal systems in participating communities.

Methods

A community-based disposal project was facilitated with assistance from community partners. The project centered on distribution of drug deactivation bags in homes and medication drop boxes at multiple healthcare facilities.

Results

The team distributed 215 drug deactivation bags to 162 community households resulting in destruction of 8011 pills, 8 medicated dermal patches and 777 mL of liquid medication. A total of 4684 pounds of medication were collected and disposed of through healthcare facility drop boxes.

Conclusion

The strategies identified are scalable and easy to replicate to meet any community's needs in reducing potential challenges of medication diversion.
Morphometric measurement of the proximal tibia to design the tibial component of total knee arthroplasty for the Thai population
Authors: Phombut Chotchuang , Rooppakhun Supakit , Sindhupakorn Bura
Published: December 2021

Purpose

This study evaluates the morphology of the Thai proximal tibia based on three-dimensional (3D) models to design the tibial component.

Methods

The 3D models of 480 tibias were created using reverse engineering techniques from computed tomography imaging data obtained from 240 volunteers (120 males, 120 females; range 20–50 years). Based on 3D measurements, a digital ruler was used to measure the distance between the triangular points of the models. The morphometric parameters consisted of mediolateral length (ML), anteroposterior width (AP), medial anteroposterior width (MAP), lateral anteroposterior width (LAP), central to a medial length (CM), central to a lateral length (CL), medial anterior radius (MAR), lateral anterior radius (LAR), and tibial aspect ratio (AR). An independent t-test was performed for gender differences, and K-means clustering was used to find the optimum sizes of the tibial component with a correlation between ML length and AP width in Thai people.

Results

The average morphometric parameters of Thai proximal tibia, namely ML, AP, MAP, LAP, CM, and CL, were as follows: 72.52 ± 5.94 mm, 46.36 ± 3.84 mm, 49.22 ± 3.62 mm, 43.59 ± 4.05 mm, 14.29 ± 2.72 mm, and 15.28 ± 2.99 mm, respectively. The average of MAR, LAR, and AR was 24.43 ± 2.11 mm, 21.52 ± 2.00 mm, and 1.57 ± 0.08, respectively. All morphometric parameters in males were significantly higher than those of females. There was a difference between the Thai proximal tibia and other nationalities and a mismatch between the size of the commercial tibial component and the Thai knee. Using K-means clustering analysis, the recommended number of ML and AP is seven sizes for the practical design of tibial components to cover the Thai anatomy.

Conclusion

The design of the tibial component should be recommended to cover the anatomy of the Thai population. These data provide essential information for the specific design of Thai knee prostheses.
Free-breathing radial 3D fat-suppressed T1-weighted gradient echo (r-VIBE) sequence for assessment of pulmonary lesions: a prospective comparison of CT and MRI
Authors: Yu Nan , Duan Haifeng , Yang Chuangbo , Yu Yong , Dang Shan
Published: December 2021

Purpose

To determine whether the pulmonary MR imaging with free-breathing radial 3D fat-suppressed T1-weighted gradient echo (r-VIBE) sequence can detect lung lesions and display lesion profiles with an accuracy comparable to that of computed tomography (CT), which is the reference standard in this study.

Population

Sixty-three consecutive patients were prospectively enrolled between October, 2016 and March, 2017. All the patients received both 3T MRI scanning with a free-breathing r-VIBE sequence and chest standard CT. Morphologic features of lesions were evaluated by two radiologists with a 5-point system. Chest standard CT were used as reference standard. Weighted kappa analysis and chi-squared test were used to determine both inter-observer agreement and inter-method agreement.

Results

A total of 210 solid pulmonary nodules or masses and 1 ground-glass nodule were detected by CT. Compared to CT, r-VIBE correctly detected 95.7% of pulmonary nodules, including 100% of detection rate with diameter greater than 6 mm, 92.3% of pulmonary nodules with diameter between 4 and 6 mm, and 83.3% of pulmonary nodules with diameter less than 4 mm The inter-method agreements between r-VIBE and standard-dose CT were either “substantial” or “excellent” in the evaluation of following features of pulmonary nodules with diameter more than 10mm: including lobulation, spiculation, convergence of vessels, bubble-like attenuation, cavitation and mediastinal lymph node enlargement (0.605≤K≤1.000; P<0.0001). However, K values for inter-method agreements were significant but “moderate” or “poor” for evaluating pleural tag, halo, and calcification (0.355≤ K≤0.451; P<0.0001).

Conclusion

The use of pulmonary MR imaging with r-VIBE showed high detection rate of pulmonary nodules and inter-method agreement with CT. It is also useful for nodule morphologic assessment.
Off-pump coronary artery bypass with heparin in a patient with a history of heparin-induced thrombocytopenia: a case report
Authors: Ito Yuya , Saito Aya , Shirai Yuki , Motomura Noboru
Published: December 2021

Background

Cardiovascular surgery for patients with a history of heparin-induced thrombocytopenia (HIT) with thrombosis requires careful perioperative anticoagulation therapy. When cardiovascular surgery is required for patients having ‘remote’ HIT, such as those who had a history of HIT and platelet factor-4/heparin antibodies turned out to be negative, it is recommended that re-exposure to heparin should be limited only to the intraoperative phase. However, few case reports have described detailed strategies for perioperative anticoagulation regimens.

Case presentation

We present the case of a 76-year-old woman, presenting with unstable angina pectoris and requiring coronary artery bypass grafting. She had a history of cardiac resuscitation and percutaneous coronary intervention for unstable angina pectoris with ventricular tachycardia 7 years prior, which caused HIT with thrombosis resulting in amputation of four fingers. On admission, platelet factor-4/heparin antibodies, biomarkers for HIT were not detected; the platelet count was 18.0 × 104/µl. Off-pump coronary artery bypass grafting was performed using heparin; argatroban infusion was continued until 9 h prior to the operation and restarted 3 h postoperatively, bridged with regular warfarin from 4 days to 3 months postoperatively. Platelet factor-4 /heparin antibodies were detected on postoperative day 8 without any clinical symptoms and became negative by day 91.

Conclusion

We consider this anticoagulation strategy is effective especially in countries, where bivalirudin is not available. Re-exposure to heparin in cardiovascular surgery for patients with a history of ‘remote HIT’ is reasonable, and appropriate anticoagulation is important for an uneventful postoperative course.