bluuebunny/crossref_metadata_2025 huggingface dataset:
Laparoscopic cholecystectomy after endoscopic trans-papillary gallbladder stenting for acute cholecystitis: a pilot study of surgical feasibility
Authors: Kawano Fumihiro , Yoshioka Ryuji , Gyoda Yu , Ichida Hirofumi , Mizuno Tomoya , Ishii Shigeto , Fujisawa Toshio , Imamura Hiroshi , Mise Yoshihiro , Isayama Hiroyuki , Saiura Akio
Published: April 2021

Background

Percutaneous transhepatic gallbladder drainage (PTGBD) is indicated for patients with acute cholecystitis (AC) who are not indicated for urgent surgery, but external tubes reduce quality of life (QOL) while waiting for elective surgery. The objective of the present study was to investigate the feasibility of laparoscopic cholecystectomy after endoscopic trans-papillary gallbladder stenting (ETGBS) comparing with after PTGBD.

Methods

Intraoperative and postoperative outcomes of patients with ETGBS and PTGBD were retrospectively compared.

Results

Eighteen ETGBS and ten PTGBD patients were compared. Differences in the duration of ETGBS and PTGBD [median 209 min (range 107–357) and median 161 min (range 130–273), respectively, P = 0.10], median blood loss [ETGBS 2 (range 2–180 ml) and PTGBD 24 (range 2–100 ml), P = 0.89], switch to laparotomy (ETGBS 11% and PTGBD 20%, P = 0.52), and median postoperative hospital stay [ETGBS 8 (range 4–24 days) and ETGBS 8 (range 4–16 days), P = 0.99]. Thickening of the cystic duct that occurred in 60% of the ETGBS patients and none of the PTGBD patients (P = 0.005) interfered with closure of the duct by clipping. No obstruction occurred in ETGBS patients.

Conclusion

ETGBS did not make laparoscopic cholecystectomy less feasible than after PTGBD. This is a pilot study, and further investigations are needed to validate the results of the present study.
Prostatic urethral lift (UroLift): a real-world analysis of outcomes using hospital episodes statistics
Authors: Page Toby , Veeratterapillay Rajan , Keltie Kim , Burn Julie , Sims Andrew
Published: April 2021

Background

To determine real-world outcomes of prostatic urethral lift (UroLift) procedures conducted in hospitals across England.

Methods

A retrospective observational cohort was identified from Hospital Episode Statistics data including men undergoing UroLift in hospitals in England between 2017 and 2020. Procedure uptake, patient demographics, inpatient complications, 30-day accident and emergency re-attendance rate, requirement for further treatment and catheterization were captured. Kaplan–Meier and hazard analysis were used to analyse time to re-treatment.

Results

2942 index UroLift procedures from 80 hospital trusts were analysed; 85.3% conducted as day-case surgery (admitted to hospital for a planned surgical procedure and returning home on the same day). In-hospital complication rate was 3.4%. 93% of men were catheter-free at 30 days. The acute accident and emergency attendance rate within 30 days was 12.0%. Results of Kaplan Meier analysis for subsequent re-treatment (including additional UroLift and endoscopic intervention) at 1 and 2 years were 5.2% [95% CI 4.2 to 6.1] and 11.9% [10.1 to 13.6] respectively.

Conclusions

This real-world analysis of UroLift shows that it can be delivered safely in a day-case setting with minimal morbidity. However, hospital resource usage for catheterization and emergency hospital attendance in the first 30 days was substantial, and 12% required re-treatment at 2 years.
Synchronous intrathyroidal parathyroid carcinoma and thyroid carcinoma: case report and review of the literature
Authors: De Falco Nadia , Santangelo Giuseppe , Chirico Fabrizio , Cangiano Angelo , Sommella Maria Giulia , Cosenza Angelo , Ronchi Andrea , Accardo Marina , Pellino Gianluca , Parmeggiani Domenico , Canonico Silvestro , De Falco Massimo
Published: April 2021

Background

Parathyroid carcinoma is a rare endocrine malignancy, rarer when synchronous with a non medullary well differentiated thyroid carcinoma. Parathyroid carcinoma accounts of 0.005% of all malignant tumors and it is responsible for less than 1% of primary hyperparathyroidism. The intrathyroidal localization of a parathyroid gland is not frequent with a reported prevalence of 0.2%. Carcinoma of parathyroids with intrathyroidal localization represents an even rarer finding, reported in only 16 cases described in literature. The rare constellation of synchronous parathyroid and thyroid carcinomas has prompted us to report our experience and perform literature review.

Case presentation

We herein report a case of a 63-years-old man with multinodular goiter and biochemical diagnosis of hyperparathyroidism. Total thyroidectomy with radio-guide technique using gamma probe after intraoperative sesta-MIBI administration and intraoperative PTH level was performed. The high radiation levels in the posterior thyroid lobe discovered an intrathyroidal parathyroid. Microscopic examination revealed a parathyroid main cell carcinoma at the posterior thyroidal left basal lobe, a classic papillary carcinoma at the same lobe and follicular variant of papillary carcinoma at the thyroidal right lobe. To the best of our knowledge, this is the first case documenting a synchronous multicentric non medullary thyroid carcinomas and intrathyroidal parathyroid carcinoma.

Conclusions

Our experience was reported and literature review underlining challenging difficulties in diagnostic workup and surgical management was carried out.
Antibacterial effect of silver diamine fluoride and potassium iodide against E. faecalis, A. naeslundii and P. micra
Authors: Briseño-Marroquín Benjamín , Ismael Yasmine , Callaway Angelika , Tennert Christian , Wolf Thomas Gerhard
Published: April 2021

Background

The aim of this study was to determine in vitro the bactericidal potential of 38% silver diamine fluoride (SDF) alone, potassium iodide (PI) alone, and the two in combination (SDF + PI) against three bacterial species commonly found in root canal samples (Enterococcus faecalis,Actinomyces naeslundiiandParvimonas micra).

Methods

The potential bactericidal rates for SDF, PI and SDF + PI againstE. faecalis,A. naeslundiiandP. micrawere calculated as reduction of bacteria colony forming units.

Results

The bactericidal potential of SDF was at 99.97–100% againstE. faecalisand 100% againstA. naeslundiiandP. micra. SDF + PI showed a 100% bactericidal effect againstP. micra, 99.89–99.98% againstE. faecalisand 99.98–100% againstA. naeslundii. The bactericidal effect of PI was 99.51–99.98% againstE. faecalis, 99.27–99.95% againstA. naeslundiiand 99.93–100% againstP. micra. The differences between controls and bacteria exposed to the antibacterial agents were statistically significant (p < 0.05).

Conclusions

SDF had an effective bactericidal effect against the examined bacteria. However, the limitations of this in vitro study do not allow a recommendation of the employment of these solutions as root canal irrigants. Additional investigations are necessary to assess their endodontic clinical applicability.
Oral myopericytoma: a rare pediatric case report and a review of the literature
Authors: Porat Ben Amy Dalit , Yaffe Victoria , Kawar Rawan , Akrish Sharon , Abu El-Naaj Imad
Published: April 2021

Background

Myopericytoma is a rare mesenchymal neoplasm with perivascular myoid differentiation that arises most commonly in middle adulthood. The lesion generally involves the subcutaneous tissue of distal extremities. Myopericytoma of the oral cavity is extremely rare. Herein we report a case of oral myopericytoma in a pediatric patient, who was treated via a conservative approach with a follow up of 8 years. The case is followed by a literature review. To our knowledge this is the first documented case of oral myopericytoma affecting a patient of such a young age.

Case presentation

A 6 years old boy was referred to the maxillofacial surgery department for the evaluation of a solitary growth of the right maxillary buccal and palatal gingiva. Histology and immunohistochemistry confirmed the diagnosis of myopericytoma.

Conclusions

Our patient was treated by local excision with no recurrence in 8 years of follow up. Conservative approach should be considered for the treatment oral myopericytoma especially in young patients in tooth bearing areas.
Atypical presentation of lateral periodontal cyst associated with impacted teeth: two case reports
Authors: Buchholzer S. , Bornert Fabien , Di Donna D. , Lombardi T.
Published: April 2021

Background

Lateral periodontal cyst (LPC) is an uncommon form of developmental odontogenic cyst. LPC can be suspected when there is a round, well-circumscribed radiolucency, usually of small diameter, along the lateral surface of vital erupted teeth, predominantly in the mandibular premolar region. Histopathological analysis allows LPC to be diagnosed based on its characteristic features such as a thin cuboidal to stratified squamous non-keratinizing epithelium containing epithelial plaques and glycogen-rich clear cells.

The aim of this article was to report two cases of atypical LPC associated either with an impacted lower left canine (tooth #33) or with a lower right third molar (tooth #48).

Case presentation

Case 1: A 56-year-old man was referred to us for an oro-dental assessment. Panoramic radiography revealed an impacted lower left permanent canine (tooth #33) with well-defined radiolucency on its upper cervical margin. A CT scan revealed a pericoronal radiolucency of 5 mm at its widest diameter around the impacted tooth #33. The pericoronal tissue was removed and sent for histopathological examination. The results revealed a lateral periodontal cyst. Satisfactory postoperative healing was achieved at the site. Follow-up at 12 months indicated no recurrence of the lesion.

Case 2: A 54-year-old woman consulted with the main issue being pain on the lower right side of the face. Intra-oral examination revealed a vestibular swelling involving the region of the second molar (tooth #47), with obliteration of buccal sulcus. Pocket depth was determined to be 9 mm at the distal of #47. A diagnosis of gingival abscess resulting from chronic periodontitis was made. Panoramic radiography revealed a radiolucent cystic lesion associated with an impacted horizontal lower right third molar (tooth #48), suggestive of a dentigerous cyst. X-rays also revealed alveolar bone resorption on the molar (tooth #47). The cyst was removed along with the third molar and submitted for histopathological diagnosis. The diagnosis was LPC. Follow-up at 18 months indicated no recurrence of the lesion.

Conclusion

These cases represent atypical presentations of LPC. They provide examples of the differential diagnosis of pericoronal radiolucencies involving an impacted tooth and our observations provide insights regarding the pathogenesis of LPC.
Factors influencing an eruption of teeth associated with a dentigerous cyst: a systematic review and meta-analysis
Authors: Nahajowski Marek , Hnitecka Sylwia , Antoszewska-Smith Joanna , Rumin Kornelia , Dubowik Magdalena , Sarul Michał
Published: April 2021

Background

A dentigerous cyst (DC) is a pathology embracing the crown of an unerupted tooth at risk of malignant transformation. The causal tooth is usually removed together with the cyst. However, if there are orthodontic contraindications for extraction, two questions arise. (1) Which factors favor spontaneous eruption? (2) Which factors imply the necessity of applying orthodontic traction? This systematic review aimed to identify factors conducive/inconducive to the spontaneous eruption of teeth after dentigerous cyst marsupialization.

Methods

In accordance with the PRISMA guidelines, the main research question was defined in the PICO format (P: patients with dentigerous cysts; I: spontaneous tooth eruption after surgical DC treatment; C: lack of a spontaneous tooth eruption after surgical DC treatment; O: determining factors potentially influencing spontaneous tooth eruption). The MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials databases were searched for keywords combining dentigerous/odontogenic/follicular cysts with teeth and/or orthodontics, as well as human teeth and eruption patterns/intervals/periods/durations. The following data were extracted from the qualified articles (4 out of 3005 found initially): the rate of tooth eruption after surgical treatment of the cyst, the age and sex of the patients, the perpendicular projection distance between the top of the tooth cusp and the edge of the alveolar process, tooth angulation, the root formation stage, the cyst area, and the eruption space. The articles were subjected to risk of bias and quality analyses with the ROBINS-I protocol and the modified Newcastle–Ottawa QAS, respectively. Meta-analyses were performed with both fixed and random effects models. The GRADE approach was used to evaluate the quality of the evidence. The systematic review was registered in PROSPERO under ID CRD42020189044.

Results

Nearly 62% of DC-associated premolars erupted spontaneously after cyst marsupialization/decompression. Young age (mean = 10 years) and root formation not exceeding 1/2 of its fully developed length were the factors likely to favor spontaneous eruption.

Conclusion

The small number of published studies, as well as their heterogeneity and the critical risk of bias, did not allow the creation of evidence-based protocols for managing teeth with DC after marsupialization. More high-quality research is needed to draw more reliable conclusions.
The hospice as a learning space: a death education intervention with a group of adolescents
Authors: Testoni Ines , Palazzo Lorenza , Ronconi Lucia , Donna Stefania , Cottone Paolo Francesco , Wieser Michael Alexander
Published: April 2021

Background

The denial of death in Western society deprives young people of the tools to derive meaning from experiences of death and dying. Literature shows that death education may allow them to become familiar with this topic without causing negative effects. This article describes the effects of a death education course with adolescents, wherein participants were given the opportunity to meet palliative doctors and palliative psychologists at school and in a hospice, where they were able to converse with the families of the dying.

Methods

This study used mixed methods and included an evaluation of a death education intervention with longitudinal follow-up of outcomes. The course involved 87 secondary school students (experimental group) aged between 16 and 20 years. We also recruited a control group of 76 similarly-aged students to observe differences. The variables we examined were: alexithymia, representation of death, value attributed to life and spirituality. These were measured with the following instruments: the Toronto Alexithymia Scale-20, the Testoni Death Representation Scale, the Personal Meaning Profile and the Spiritual Orientation Inventory, respectively. To better understand how the students perceived the experience, we asked the experimental group to answer some open-ended questions. Their answers were analysed through thematic analysis.

Results

The study showed that death education and the hospice experience did not produce negative effects, but rather allowed students to decrease alexithymia, improving their ability to recognise and express emotions. Thematic analysis revealed that all participants perceived the experience as very positive.

Conclusions

Our findings affirm that death education programs can be successfully implemented in high schools, and that they can usefully involve local hospices and palliative care professionals, especially physicians and psychologists.
Co-electrospun nanofibrous mats loaded with bitter gourd (Momordica charantia) extract as the wound dressing materials: in vitro and in vivo study
Authors: Salami Mohammad Saeid , Bahrami Gholamreza , Arkan Elham , Izadi Zhila , Miraghaee Shahram , Samadian Hadi
Published: April 2021

Background

Interactive dressings are innovatively designed to interact with the wound surface and alter the wound environment to promote wound healing. In the current study, we integrated the physicochemical properties of Poly (caprolactone)/ Poly (vinyl alcohol)/Collagen (PCL/PVA/Col) nanofibers with the biological activities ofMomordica charantiapulp extract to develop an efficient wound dressing. The electrospinning method was applied to fabricate the nanofibers, and the prepared wound dressings were thoroughly characterized.

Results

SEM imaging showed that the nanofibers were uniform, straight, without any beds with a diameter in the range of 260 to 480 nm. Increasing the concentration of the extract increased the diameter of the nanofibers and also the wettability characteristics while reduced the ultimate tensile strength from 4.37 ± 0.90 MPa for PCL/PVA/Col to 1.62 ± 0.50 MPa for PCL/PVA/Col/Ex 10% (p < 0.05). The in vivo studies showed that the application of the wound dressings significantly enhanced the healing process and the highest wound closure, 94.01 ± 8.12%, was obtained by PCL/PVA/Col/Ex 10% nanofibers (p < 0.05).

Conclusion

The incorporation of the extract had no significant effects on nanofibers’ porosity, water vapor permeability, and swelling characteristics. The in vitro evaluations showed that the fabricated nanofibers were hemocompatible, cytocompatible, and prevent bacterial penetration through the dressing. These findings implied that the PCL/PVA/Col/Ex nanofibers can be applied as the wound dressing materials.
Contextual property detection in Dutch diagnosis descriptions for uncertainty, laterality and temporality
Authors: Klappe Eva S. , van Putten Florentien J. P. , de Keizer Nicolette F. , Cornet Ronald
Published: April 2021

Background

Accurate, coded problem lists are valuable for data reuse, including clinical decision support and research. However, healthcare providers frequently modify coded diagnoses by including or removing common contextual properties in free-text diagnosis descriptions: uncertainty (suspected glaucoma), laterality (left glaucoma) and temporality (glaucoma 2002). These contextual properties could cause a difference in meaning between underlying diagnosis codes and modified descriptions, inhibiting data reuse. We therefore aimed to develop and evaluate an algorithm to identify these contextual properties.

Methods

A rule-based algorithm called UnLaTem (Uncertainty, Laterality, Temporality) was developed using a single-center dataset, including 288,935 diagnosis descriptions, of which 73,280 (25.4%) were modified by healthcare providers. Internal validation of the algorithm was conducted with an independent sample of 980 unique records. A second validation of the algorithm was conducted with 996 records from a Dutch multicenter dataset including 175,210 modified descriptions of five hospitals. Two researchers independently annotated the two validation samples. Performance of the algorithm was determined using means of the recall and precision of the validation samples. The algorithm was applied to the multicenter dataset to determine the actual prevalence of the contextual properties within the modified descriptions per specialty.

Results

For the single-center dataset recall (and precision) for removal of uncertainty, uncertainty, laterality and temporality respectively were 100 (60.0), 99.1 (89.9), 100 (97.3) and 97.6 (97.6). For the multicenter dataset for removal of uncertainty, uncertainty, laterality and temporality it was 57.1 (88.9), 86.3 (88.9), 99.7 (93.5) and 96.8 (90.1). Within the modified descriptions of the multicenter dataset, 1.3% contained removal of uncertainty, 9.9% uncertainty, 31.4% laterality and 9.8% temporality.

Conclusions

We successfully developed a rule-based algorithm named UnLaTem to identify contextual properties in Dutch modified diagnosis descriptions. UnLaTem could be extended with more trigger terms, new rules and the recognition of term order to increase the performance even further. The algorithm’s rules are available as additional file 2. Implementing UnLaTem in Dutch hospital systems can improve precision of information retrieval and extraction from diagnosis descriptions, which can be used for data reuse purposes such as decision support and research.
The predictive role of sickness absence spell durations in associations with inpatient- and specialized outpatient care among a population-based Swedish twin sample
Authors: Ropponen Annina , Wang Mo , Narusyte Jurgita , Kärkkäinen Sanna , Blom Victoria , Svedberg Pia
Published: April 2021

Background

The associations between a sickness absence spell duration and patient care have been rarely studied. An assumption is that associations would differ by spell duration and by the patient care type, inpatient- or specialized outpatient, due to severity of diseases and/or conditions. We aimed to investigate sickness absence spells in various spell durations as a predictor for subsequent inpatient- and specialized outpatient care separately, and to study if familial confounding plays a role in these associations.

Methods

We followed a population-based sample of Swedish twins born 1925–90 with national registers from 2001 for first incident sickness absence spell (days to calculate spell duration categorized into ≤30 days, 31–90 days, 91–180 days and ≥ 181 days), or no sickness absence, and for inpatient- and specialized outpatient care until 2013 (n = 24,975). Cox proportional hazards models were applied for hazard ratios (HR) with 95% confidence intervals (CI) while accounting for covariates and familial confounding.

Results

First incident sickness absence spell across all duration categories was associated with an increased risk of inpatient- (age- and sex adjusted HR 1.28 to 6.05) or specialized outpatient care (HR 1.17–2.50), both in comparison to those without any sickness absence or the shortest sickness absence spell category (1–30 days). The associations remained statistically significant while controlling for covariates or familial confounding.

Conclusions

First incident sickness absence spell increases the risk of inpatient care or specialized outpatient care regardless of the duration of the sickness absence spell. Hence, incident sickness absence spells should be noted and targeted to actions at workplaces as well as in primary and occupational health care.
Determinants of health care use among homeless individuals: evidence from the Hamburg survey of homeless individuals
Authors: Hajek André , Bertram Franziska , Heinrich Fabian , van Rüth Victoria , Ondruschka Benjamin , Kretzler Benedikt , Schüler Christine , Püschel Klaus , König Hans-Helmut
Published: April 2021

Background

To identify the determinants of health care use among homeless individuals.

Methods

Data were taken from the Hamburg survey of homeless individuals (n = 100 individuals in the here used model, mean age 44.8 years, SD 12.5) focusing on homeless individuals in Hamburg, Germany. The number of physician visits in the past 3 months and hospitalization in the preceding 12 months were used as outcome measures. Drawing on the Andersen model of health care use as a conceptual framework, predisposing characteristics, enabling resources and need factors as well as psychosocial variables were included as correlates.

Results

Negative binomial regressions showed that increased physician visits were associated with being female (IRR: 4.02 [95% CI: 1.60–10.11]), absence of chronic alcohol consume (IRR: 0.26 [95% CI: 0.12–0.57]) and lower health-related quality of life (IRR: 0.97 [95% CI: 0.96–0.98]). Furthermore, logistic regressions showed that the likelihood of hospitalization was positively associated with lower age (OR: 0.93 [95% CI: 0.89–0.98]), having health insurance (OR: 8.11 [2.11–30.80]) and lower health-related quality of life (OR: 0.97 [95% CI: 0.94–0.99]).

Conclusions

Our study showed that predisposing characteristics (both age and sex), enabling resources (i.e., health insurance) and need factors in terms of health-related quality of life are main drivers of health care use among homeless individuals. This knowledge may assist in managing health care use.
Victorian healthcare experience survey 2016–2018; evaluation of interventions to improve the patient experience
Authors: Wong Eunice , Mavondo Felix , Horvat Lidia , McKinlay Louise , Fisher Jane
Published: April 2021

Background

Patient experience is recognised as a quality of care indicator and increasingly health services are working on achieving set targets and improving their performance. Interventions at the point of care targeting communication with patients, patient engagement in care processes and discharge planning are associated with better patient experience. However, their efficacy and application to different contexts are still unclear. The aims were to describe the interventions implemented by health services to improve patient experience, their impact on overall patient experiences and specific experiences in areas of communication, discharge planning, patient education on treatment/tests, the physical environment and access to care.

Methods

Secondary data analysis of the Victorian Healthcare Experience inpatient surveys reported in September 2016 and 2018 and content analysis of interventions published in the Victorian Quality Account for 2017 from 59 public health services in Victoria, Australia. The interventions were categorised using an adapted taxonomy of professional interventions by the Cochrane EPOC Review Group. Univariate tests and confirmatory factor analysis were conducted to test measure invariance across the 2016 and 2018 groups and examine the association between each of the intervention categories on overall patient experience measure and specific outcome measures.

Results

This study found that the overall patient experience was consistent (93%) between 2016 and 2018 samples. In comparing impact, a single intervention rather than none or multiple interventions in communication, respect and dignity and treatment and disease education areas were associated with a higher level of the overall patient experience. Interventions in waiting time, access to service, care continuity and emotional support categories were associated with a decrease in overall patient experience.

Conclusion

This study found that to improve the overall patient experience, more focus is needed on evidence-based interventions in dignity and respect and emotional support. Furthermore, the choice of interventions should be guided by evidence of their efficacy and prioritising implementing one intervention well, provides more gains.
Toceranib phosphate-associated nephrotic syndrome in a dog: a case report
Authors: Remerowski Shannon M. , Herrera Chamisa L. , Donnelly Lindsay L.
Published: April 2021

Background

Nephrotic syndrome (NS) is rare in dogs and is characterized by concurrent clinical findings of proteinuria, hyperlipidemia, hypoalbuminemia, and edema. NS has been reported in humans receiving tyrosine kinase inhibitors (TKI) and in dogs receiving masitinib. This is the first report of NS in a dog receiving toceranib phosphate.

Case presentation

An 8-year-old, female, spayed Labrador retriever was diagnosed with a 10 cm mast cell tumor on the left lateral abdomen. After completion of a 12-week vinblastine and prednisone protocol, she began treatment with toceranib phosphate (2.6 mg/kg by mouth, every other day). Proteinuria was documented prior to starting toceranib. On day 426 after diagnosis (day 328 of toceranib phosphate treatment), the dog was evaluated for diarrhea, lethargy and anorexia. On physical examination, dependent edema was noted on the ventral chest and abdomen, and sterile neutrophilic inflammation was aspirated from a 2.3 cm splenic nodule. The following laboratory values were reported: albumin < 1.5 g/dL; cholesterol 378 mg/dl and urine protein to creatinine ratio of 3.79. The patient was diagnosed with NS, and treatment with toceranib phosphate was discontinued. Low-dose aspirin was started in addition to an increased dosage of enalapril (0.47 mg/kg q12hr). No other therapy was instituted. The dog improved clinically, and laboratory values returned to near normal over the 8-week follow-up. She was euthanized 1399 days after discontinuing toceranib phosphate with progressive disease.

Conclusions

Nephrotic syndrome is a potential adverse event associated with the drug toceranib phosphate which may be reversible with discontinuation of treatment. Careful monitoring of urine protein, serum biochemistry, blood pressure and patient weight is advisable during treatment with toceranib phosphate.
Biochemical and synergistic properties of a novel alpha‐amylase from Chinese nong‐flavor Daqu
Authors: Chen Lanchai , Yi Zhuolin , Fang Yang , Jin Yanling , He Kaize , Xiao Yao , Zhao Dong , Luo Huibo , He Hui , Sun Qun , Zhao Hai
Published: April 2021

Background

Daqu is the most important fermentation starter for Chinese liquor, with large number of microbes and enzymes being openly enriched in the Daqu system over thousands of years. However, only a few enzymes have been analyzed with crude protein for total liquefying power and saccharifying power of Daqu. Therefore, the complex enzymatic system present in Daqu has not been completely characterized. Moreover, their pivotal and complicated functions in Daqu are completely unknown.

Results

In this study, a novel α-amylase NFAmy13B, from GH13_5 subfamily (according to the Carbohydrate-Active enZYmes Database, CAZy) was successfully heterologous expressed by Escherichia coli from Chinese Nong-flavor (NF) Daqu. It exhibited high stability ranging from pH 5.5 to 12.5, and higher specific activity, compared to other GH13_5 fungal α-amylases. Moreover, NFAmy13B did not show activity loss and retained 96% residual activity after pre-incubation at pH 11 for 21 h and pH 12 for 10 h, respectively. Additionally, 1.25 mM Ca2+ significantly improved its thermostability. NFAmy13B showed a synergistic effect on degrading wheat starch with NFAmy13A (GH13_1), another α-amylase from Daqu. Both enzymes could cleave maltotetraose and maltopentaose in same degradation pattern, and only NFAmy13A could efficiently degrade maltotriose. Moreover, NFAmy13B showed higher catalytic efficiency on long-chain starch, while NFAmy13A had higher catalytic efficiency on short-chain maltooligosaccharides. Their different catalytic efficiencies on starch and maltooligosaccharides may be caused by their discrepant substrate-binding region.

Conclusions

This study mined a novel GH13_5 fungal α-amylase (NFAmy13B) with outstanding alkali resistance from Nong-flavor (NF) Daqu. Furthermore, its synergistic effect with NFAmy13A (GH13_1) on hydrolyzing wheat starch was confirmed, and their possible contribution in NF Daqu was also speculated. Thus, we not only provide a candidate α-amylase for industry, but also a useful strategy for further studying the interactions in the complex enzyme system of Daqu.
Phosphonates enantiomers receiving with fungal enzymatic systems
Authors: Serafin-Lewańczuk Monika , Brzezińska-Rodak Małgorzata , Lubiak-Kozłowska Katarzyna , Majewska Paulina , Klimek-Ochab Magdalena , Olszewski Tomasz K. , Żymańczyk-Duda Ewa
Published: April 2021

Background

Phosphonates derivatives are in the area of interests because of their unique chemical-physical features. These compounds manifest variety of biological interactions within the sensitive living cells, including impact on particular enzymes activities. Biological “cause and effect” interactions are based upon the specific matching between the structures and/or compounds and this is usually the result of proper optical configurations of particular chiral moieties. Presented research is targeted to the phosphonates with the heteroatom incorporated in their side functionalities. Such molecules are described as possible substrates of bioconversion for the first time lately and this field is not fully explored.

Results

Presented research is targeted to the synthesis of pure hetero-phosphonates enantiomers. The catalytic activity of yeasts and moulds were tested towards two substrates: the thienyl and imidazole phosphonates to resolve their racemic mixtures. Biotransformations conditions differed depending on the outcome, what included changing of following parameters: type of cultivation media, bioprocess duration (24–72 h), additional biocatalyst pre-treatment (24–48 h starvation step triggering the secondary metabolism). (S)-1-amino-1-(3-thienyl)methylphosphonate was produced with the assistance of R. mucilaginosa or A. niger (e.e. up to 98% and yield up to 100%), starting from the 3 mM of substrate racemic mixture. Bioconversion of racemic mixture of 3 mM of (1-amino-1-(4-imidazole)methylphosphonic acid) resulted in the synthesis of S-isomer (up to 95% of e.e.; 100% of yield) with assistance of R. mucilaginosa. 24 h biotransformation was conducted with biomass preincubated under 48-hour starvation conditions. Such stereoselective resolution of the racemic mixtures of substrates undergoes under kinetic control with the conversion of one from the enantiomers.

Conclusions

Composition of the culturing media and pre-incubation in conditions of nutrient deficiency were significant factors influencing the results of kinetic resolution of racemic mixtures of phosphonic substrates and influencing the economic side of the biocatalysis e.g. by determining the duration of whole biocatalytic process.

Graphical abstract
Down-regulation of cylindromatosis protein phosphorylation by BTK inhibitor promotes apoptosis of non-GCB-diffuse large B-cell lymphoma
Authors: Xu Xin , Wei Ting , Zhong Weijie , Ang Rosalind , Lei Ye , Zhang Hui , Li Qingshan
Published: April 2021

Background

Non-germinal center B-cell-like diffuse large B-cell lymphoma (non-GCB-DLBCL) has worse clinical outcome than GCB-DLBCL, and some relapsed/refractory non-GCB-DLBCL (R/R non-GCB-DLBCL) are even resistant to CD20 monoclonal antibody (rituximab). Bruton’s tyrosine kinase inhibitors (BTKis) are new drugs for B-cell lymphoma. BTKis can promote apoptosis of DLBCL by inactivating nuclear transcription factor κB (NFκB) signaling pathway. Cylindromatosis (CYLD) is a tumor suppressor and ubiquitinase. CYLD can inactivate NFκB signaling pathway through ubiquitination and regulate the apoptosis of hematological tumors. The ubiquitination of CYLD can be regulated by phosphorylation, suggesting that the regulation of CYLD phosphorylation can be a potential mechanism to promote the apoptosis of hematological tumors. Therefore, we hypothesized that BTKis could promote the apoptosis of non-GCB-DLBCL by regulating the phosphorylation of CYLD, especially in rituximab resistant cases, and we proved this hypothesis through both in vivo and in vitro experiments.

Methods

The baseline expression levels of CYLD phosphorylation in non-GCB-DLBCL patients and cell lines were detected by Western Blotting. The non-GCB-DLBCL cell lines were treated with BTKis, and apoptosis induced by BTKis treatment was detected by Western blotting, cell viability assay and Annexin V assay. To verify whether the effect of BTKis on apoptosis in non-GCN-DLBCL cells is CYLD dependent, the expression of CYLD was knocked down by lentiviral shRNAs. To verify the effect of BTKis on the phosphorylation of CYLD and the apoptosis in vivo and in rituximab resistant non-GCB-DLBCL, the xeograft model and rituximab resistant non-GCB-DLBCL cells were generated by tumor cell inoculation and escalation of drug concentrations, respectively.

Results

BTKis induced apoptosis by down-regulating CYLD phosphorylationin in non GCB-DLBCL, xenograft mouse model, and rituximab-resistant cells, and this effect could be enhanced by rituximab. Knocking-down CYLD reversed apoptosis which was induced by BTKis. BTKis induced CYLD-dependent apoptosis in non-GCB-DLBCL including in rituximab-resistant cells.

Conclusions

The present results indicated that CYLD phosphorylation is a potential clinical therapeutic target for non-GCB-DLBCL, especially for rituximab-resistant relapsed/refractory cases.
Role of tumor mutation burden-related signatures in the prognosis and immune microenvironment of pancreatic ductal adenocarcinoma
Authors: Tang Rong , Liu Xiaomeng , Wang Wei , Hua Jie , Xu Jin , Liang Chen , Meng Qingcai , Liu Jiang , Zhang Bo , Yu Xianjun , Shi Si
Published: April 2021

Background

High tumor mutation burden (TMB) has gradually become a sensitive biomarker for predicting the response to immunotherapy in many cancers, including lung, bladder and head and neck cancers. However, whether high TMB predicts the response to immunotherapy and prognosis in pancreatic ductal adenocarcinoma (PDAC) remained obscure. Hence, it is significant to investigate the role of genes related to TMB (TRGs) in PDAC.

Methods

The transcriptome and mutation data of PDAC was downloaded from The Cancer Genome Atlas-Pancreatic Adenocarcinoma (TCGA). Five independent external datasets of PDAC were chosen to validate parts of our results. qRT-PCR and immunohistochemical staining were also performed to promote the reliability of this study.

Results

The median overall survival (OS) was significantly increased in TMB_low group compared with the counterpart with higher TMB score after tumor purity adjusted (P = 0.03). 718 differentially expressed TRGs were identified and functionally enriched in some oncogenic pathways. 67 TRGs were associated with OS in PDAC. A prognostic model for the OS was constructed and showed a high predictive accuracy (AUC = 0.849). We also found TMB score was associated with multiple immune components and signatures in tumor microenvironment. In addition, we identified a PDAC subgroup featured with TMBlowMicrosatellite instabilityhigh(MSIhigh) was associated with prolonged OS and a key molecule, ANKRD55, potentially mediating the survival benefits.

Conclusion

This study analyzed the biological function, prognosis value, implications for mutation landscape and potential influence on immune microenvironment of TRGs in PDAC, which contributed to get aware of the role of TMB in PDAC. Future studies are expected to investigate how these TRGs regulate the initiation, development or repression of PDAC.
Hereditary angioedema due to C1 inhibitor deficiency in Belarus: epidemiology, access to diagnosis and seven novel mutations in SERPING1 gene
Authors: Guryanova Irina , Suffritti Chiara , Parolin Debora , Zanichelli Andrea , Ishchanka Nastassia , Polyakova Ekaterina , Belevtsev Mikhail , Perego Francesca , Cicardi Marco , Zharankova Yulia , Konoplya Natalya , Caccia Sonia , Gidaro Antonio
Published: April 2021

Background

Hereditary angioedema due to C1 inhibitor deficiency (C1-INH-HAE) is a rare disease. Few states in developing countries have an adequate management of HAE, but none of them belongs to the former USSR area. This study analyses data from C1-INH-HAE patients from Belarus.

Methods

Data about clinical characteristics, genetics, access to diagnosis and treatment were collected from 2010 by the Belarusian Research Center for Pediatric Oncology, Hematology and Immunology in Minsk. A questionnaire about attacks, prophylactic (LTP) and on-demand therapy (ODT) was administered to patients.

Results

We identified 64 C1-INH-HAE patients belonging to 26 families, 27 (42.2%) of which were diagnosed in the last 3 years. The estimated minimal prevalence was 1:148,000. Median age at diagnosis was 29 years, with diagnostic delay of 19 years. Thirty-eight patients answered a questionnaire about therapy. Eleven patients did not use any treatment to resolve HAE attacks. Twenty-seven patients underwent ODT: 9 with appropriate treatments, and 18 with inappropriate treatments. Nine patients used LTP with attenuated androgens and 1 with tranexamic acid. Thirty-two patients answered a questionnaire about attacks and triggers: 368 angioedema attacks were reported, with an average of 10 attacks per year. We found 24 different SERPING1 variants: 9 missenses, 6 in splice sites, 6 small deletions, 2 nonsense, 1 large deletion; 7 have not been previously described. De novo variants were found in 11 patients.

Conclusions

C1-INH-HAE diagnosis and management in Belarus is improved as seen from the high number of new diagnosis in the last 3 years. Next steps will be to reduce the diagnostic delay and to promote the LTP and ODT.
Ethical and legal issues in psychedelic harm reduction and integration therapy
Authors: Pilecki Brian , Luoma Jason B. , Bathje Geoff J. , Rhea Joseph , Narloch Vilmarie Fraguada
Published: April 2021

Psychedelic-assisted therapy may represent an upcoming paradigm shift in the treatment of mental health problems as recent clinical trials have demonstrated strong evidence of their therapeutic benefits. While psychedelics are currently prohibited substances in most countries, the growing popularity of their therapeutic potential is leading many people to use psychedelics on their own rather than waiting for legal medical access. Therapists therefore have an ethical duty to meet this need by providing support for clients using psychedelics. However, incorporating psychedelics into traditional psychotherapy poses some risk given their prohibited status and many therapists are unsure of how they might practice in this area. This paper explicates such risks and describes ways in which therapists can mitigate them and strive to practice within legal and ethical boundaries. A harm reduction approach will be emphasized as a useful framework for conducting therapy around clients' use of psychedelics. It is argued that therapists can meet with clients before and after their own personal psychedelic experiences in order to help clients minimize risk and maximize benefit. Common clinical scenarios in this growing clinical area will also be discussed.
Intragenerational social mobility and self-rated oral health in the british cohort study
Authors: Mohd Khairuddin Aina Najwa , Bernabé Eduardo , Delgado-Angulo Elsa Karina
Published: April 2021

Background

Most studies on social mobility and oral health have focused on movement between generations (intergenerational mobility) rather than movement within an individual’s own lifetime (intragenerational mobility). The aim of this study was to investigate the association between intragenerational social mobility from early to middle adulthood and self-rated oral health.

Methods

This study used data from 6524 participants of the 1970 British Birth Cohort Study, an ongoing population-based birth cohort of individuals born in England, Scotland and Wales. Participants’ socioeconomic position was indicated by occupational social class at age 26 and 46 years (the first and latest adult waves, respectively). Self-rated oral health was measured at age 46 years. The association between social mobility and adult oral health was assessed using conventional regression models and diagonal reference models, adjusting for gender, ethnicity, country of residence and residence area.

Results

Over a fifth of participants (22.2%) reported poor self-rated oral health at age 46 years. In conventional regression analysis, the odds ratios for social mobility varied depending on whether they were adjusted for social class of origin or destination. In addition, all social trajectories had greater odds of reporting poor oral health than non-mobile adults in class I/II. In diagonal reference models, both upward (Odds Ratio 0.79; 95% CI 0.63–0.99) and downward mobility (0.90; 95% CI 0.71–1.13) were inversely associated with poor self-rated oral health. The origin weight was 0.48 (95% CI 0.33–0.63), suggesting that social class of origin was as important as social class of destination.

Conclusion

This longitudinal analysis showed that intragenerational social mobility from young to middle adulthood was associated with self-rated oral health, independent of previous and current social class.
Enabling visibility of the clinician-scientists’ knowledge broker role: a participatory design research in the Dutch nursing-home sector
Authors: Barry Margot , Kuijer Wietske , Persoon Anke , Nieuwenhuis Loek , Scherpbier Nynke
Published: April 2021

Background

A group of clinician-scientists and managers working within a Dutch academic network, experienced difficulties in clearly defining the knowledge broker role of the clinician-scientists. They found no role clarity in literature, nor did they find tools or methods suitable for clinician-scientists. Clarifying role expectations and providing accountability for funding these knowledge broker positions was difficult. The aim of this research was to design a theory-informed tool that allowed clinician-scientists to make their knowledge broker role visible.

Methods

A participatory design research was conducted in three phases, over a 21-month period, with a design group consisting of an external independent researcher, clinician-scientists and their managers from within the academic network. Phase 1 constituted a literature review, a context analysis and a needs analysis. Phase 2 constituted the design and development of a suitable tool and phase 3 was an evaluation of the tool’s perceived usefulness. Throughout the research process, the researcher logged the theoretic basis for all design decisions.

Results

The clinician-scientist’s knowledge broker role is a knowledge-intensive role and work-tasks associated with this role are not automatically visible (phase 1). A tool (the SP-tool) was developed in Microsoft Excel. This allowed clinician-scientists to log their knowledge broker activities as distinct from their clinical work and research related activities (phase 2). The SP-tool contributed to the clinician-scientists’ ability to make their knowledge broker role visible to themselves and their stakeholders (phase 3). The theoretic contribution of the design research is a conceptual model of professionalisation of the clinician-scientist’s knowledge broker role. This model presents the relationship between work visibility and the clarification of functions of the knowledge broker role. In the professionalisation of knowledge-intensive work, visibility contributes to the definition of clinician-scientists broker functions, which is an element necessary for the professionalisation of an occupation.

Conclusions

The SP-tool that was developed in this research, contributes to creating work visibility of the clinician-scientists’ knowledge broker role. Further research using the SP-tool could establish a clearer description of the knowledge broker role at the day-to-day professional level and improved ability to support this role within organisations.
The “Great Debate” at Immunotherapy Bridge 2020, December 3rd, 2020
Authors: Ascierto Paolo A. , Brody Joshua , Butterfield Lisa H. , Finn Olivera J. , Goldberg John , Perrone Francesco , Sullivan Ryan J. , Fox Bernard A. , Hwu Patrick , Puzanov Igor
Published: April 2021

As part of the 2020 Immunotherapy Bridge virtual congress (December 2nd–3rd, Italy), the Great Debate session featured counterpoint views from leading experts on three clinical questions in immunotherapy today. The first of these was whether antitumoral vaccination is still a treatment option. The second topic debated whether anti-programmed death (PD)-1/PD-ligand (L)1 blockade should be the backbone for immunotherapy combination. Finally, the use of innovative study designs and surrogate endpoints was considered from both an academic and industry perspective. For each topic, two experts presented the argument and counter-argument in support of two different points of view. As with previous Bridge congresses, the debates were assigned by meeting Chairs and positions taken by experts during the debates may not have necessarily reflected their respective personal view. The views summarised in this article are based on available evidence but may reflect personal interpretation of these data, clinical experience and subjective opinion of the speaker.