bluuebunny/crossref_metadata_2025 huggingface dataset:
HDAC and HLA Class I expression in uveal melanoma
Authors: Souri Zahra , Verdijk Rob , Luyten Gregorius , Jager Martine
Published: January 2021

Purpose

Histone deacytylases (HDACs) can be a target for therapy in oncology. We determined the expression of four families of HDACs in Uveal Melanoma (UM) to see whether expression differed between low‐ and high‐risk tumors and whether their expression is related to survival.

Methods

The expression of nine HDAC’s was determined using an Illumina HT12V4 array in 64 primary UM. Tumors were divided into BAP1‐positive or ‐negative based on immune‐histochemical nuclear staining. Survival status was determined using Kaplan‐Meier analyses, using the time period between enucleation and death (mean 83 months).

Results

High‐risk BAP1‐negative UM (n = 30) showed a higher expression of HDAC4 (p = 0.003), HDAC7 (p = 0.02), and HDAC8 (p ≤ 0.001), and a decreased expression of HDAC11 (p ≤ 0.001) compared to BAP1‐positive UM (n = 25). When analyzing survival, we found that a high HDAC8 (p = 0.002) and low HDAC11 (p = 0.002) expression were associated with a lower overall survival.

Conclusions

As HDAC’s are being used as targets for cancer therapy, we studied the expression of a range of them in UM and identified upregulated expression of two of these epigenetic regulators in high‐risk BAP1‐negative tumors, and a down‐regulated expression of one (HDAC11). Our findings indicate that pan‐HDAC inhibitors differentially affect different HDACs and may specifically be useful for those with BAP1‐negative tumors.
Smart connected devices to objectively assess the adherence to eyedrops
Authors: Renault Didier , Courrier Emilie , Trone Marie Caroline , Gauthier Anne Sophie , Garcin Thibaud , Rebika Hayette , Thuret Gilles , Gain Philippe
Published: January 2021

Purpose

Compliance issues are often reported in ophthalmology for glaucoma which is one of the leading causes of blindness and visual disability and for dry eye syndrome (DES) requiring multiple frequent instillations. The smart electronic devices have emerged as one of the most reliable means of improving adherence to treatment, allowing objective quantification of the taken treatments. Aim: to report the pilot use in DES of two new electronic devices designed for the monitoring of adherence to eye drop medications.

Methods

The KaliDROP for eye drop bottles, and the KaliJAR for single‐dose‐units (SDU; Kali‐CARE, Santa Clara, CA, USA) were 3G wireless devices that recorded and transmitted in real respectively the number of instillations (when the bottle in pressed and reversed) and the number of SDU discarded after use. Both were tested by one of the author suffering from DES. The Kali Drop was tested during 28 consecutive days with an ABAK bottle of Thealose (Thea laboratories). The KaliJAR was tested during 47 consecutive days with SDU of Thealoz Duo Gel (Thea laboratories). In parallel, he noted on paper the date and time of each eye drop instillation. The agreement with the data recorded in the software was analyzed.

Results

On the 354 instillations noted on paper, 352 (99.4%) were recorded by the KaliDROP device. Two instillations were not recorded, and one instillation was wrongly detected. On the 2200 SDUs introduced in the KaliJAR, 2136 (97.1%) were recorded. 64 SDUs (2.9%) were not recorded but none was wrongly detected. This percentage of false negative could be explained by the fact that 30–50 SDUs were inserted immediately one after the other. The number of undetected SDU would be virtually null if each SDU was discarded separately as normally recommended.

Conclusions

These two innovative simple‐to‐use devices could find strong applications in therapeutic education and clinical trials.
Survival analysis of inherited retinoblastoma: a population‐based analysis, 1975–2011
Authors: Yassa Arsany , Mikhael Sandra , Tadrosse Abanoob , Mikhael Mina , Eloy Jean‐Anderson
Published: January 2021

Purpose

To study the survival patterns of inherited Retinoblastoma.

Methods

A retrospective, population‐based analysis was conducted on children younger than 5 years old using the Surveillance, Epidemiology, and End Results Registry from 1975 to 2011. Bilateral cases (BL) were used as a proxy for inherited ones. Kaplan–Meir analysis was used to calculate 5‐year overall survival (5yOS).

Results

Four hundred fifty‐three cases were identified. 5yOS was 93.3%. There was no significant difference in 5yOS between sexes (p = 0.72), among white, black and other races (p = 0.17) or among patients diagnosed during the first, second and third years of life (p = 0.453). Survival based on staging was: localized (95.8%), regional (83.7%), distant (91.6%) (p < 0.01). 5yOS during the interval 1975–1990 (87.0%) was significantly lower than during the interval 1996–2011 (95.5%) (p < 0.01).

Conclusions

Survival of inherited retinoblastoma is not affected by sex, race or age at diagnosis. Staging is a prognostic factor for survival. Survival shows improvement over the timeframe studied.

Bibliography

Surveillance Research Program, National Cancer Institute SEER*Stat software (seer.cancer.gov/seerstat) version 8.3.6.
Resveratrol nanoparticles are neuroprotective in a model of multiple sclerosis
Authors: Shamsher Ehtesham , Khan Reas S. , Dine Kimberly , Luong Vy , Davis Benjamin M. , Willett Keirnan , Somavarapu Satyanarayana , Francesca Cordeiro M. , Shindler Kenneth S.
Published: January 2021

Purpose

Optic neuritis is the most common clinical manifestation of multiple sclerosis. Axonal damage and neuronal loss lead to permanent neurological disability in patients and its animal model, experimental autoimmune encephalomyelitis (EAE). Presently, treatments of this condition aim to reduce inflammation without showing any neuroprotection. Resveratrol is a natural polyphenol found in red wine with neuroprotective effects but poor solubility in water. Thus, a novel nanoparticle formulation of resveratrol was developed and assessed in a mouse model of EAE.

Methods

Resveratrol nanoparticles (RNs) were formulated using a thin rehydration technique and assessed for stability with spectrophotometric techniques. C57/BL6 mice were immunized with the myelin oligodendroglial glycoprotein peptide. From EAE induction, mice were treated daily for 30 days by oral gavage of RNs (n = 6), vehicle (n = 5) or unconjugated resveratrol (UnRSV); n = 6). Mice were assessed for EAE signs daily and for visual function weekly by optokinetic responses (OKR). Optic nerve and spinal cord inflammation were assessed by hematoxylin and eosin (H&E). Retinal ganglion cells were immunostained with Brn3a.

Results

Resveratrol nanoparticles (RNs) containing >10 mg/ml resveratrol were stable over 3 months with an encapsulation efficiency >70%. 16.9 mg/kg RNs reduced the EAE clinical score at day 30 compared to 16.9 mg/kg vehicle (1.4 ± 0.4 versus 3.0 ± 0.4, p < 0.05) whereas up to 100 mg/kg UnRSV did not lead to reduction of EAE scores. OKR, optic nerve inflammation and spinal cord inflammation were not significantly modified by oral administration of RNs. 16.9 mg/kg RNs reduced RGC loss compared to 16.9 mg/kg vehicle (347 ± 12 versus 172 ± 12 cells/standardized field, p < 0.0001). Importantly, to get a similar reduction, at least 100 mg/kg of UnRSV were needed suggesting that RNs increase resveratrol bioavailability.

Conclusions

Resveratrol nanoparticles (RNs) increase resveratrol solubility and bioavailability. They show neuroprotection by reducing RGC loss. However, as previously reported for resveratrol, these nanoparticles do not have any anti‐inflammatory effect.
The information content of target price forecasts: Evidence from mergers and acquisitions
Authors: Ho Tuan , Brownen‐Trinh Ruby , Xu Fangming
Published: January 2021

This paper investigates the informativeness and value relevance of analyst target prices in the context of mergers and acquisitions. Our results indicate that firms with high 12‐month ahead target prices relative to current stock prices are more likely to become a takeover target and offer premium, and acquirers’ announcement returns are positively associated with firms’ target price premium. We also show that a long‐short trading strategy formed on target prices and firms’ takeover likelihood generates economically significant returns. Our results are robust to a battery of additional analysis, and the informativeness of target prices is not subsumed by other analyst forecast outputs such as earnings forecasts and recommendations. Overall, our findings suggest that analysts convey valuable information through target price forecasts, which are useful for participants in the corporate takeover markets.
Factors affecting non‐adherence to medical appointments among patients with hypertension at public health facilities in Punjab, India
Authors: Das Bidisha , Neupane Dinesh , Singh Gill Sandeep , Bir Singh Gurinder
Published: January 2021

Daily adherence to antihypertensive medications is necessary to control hypertension. Under the State hypertension control program, hypertensive patients are enrolled in public health settings, provided with 30‐day medication prescriptions, and advised to return to the health facility monthly. However, at least 50‐60% of patients do not visit the health facility for their scheduled follow‐up appointments. The authors aimed to document the major reasons for missed appointments and to characterize patient and health system barriers. By telephone, the authors interviewed 300 randomly selected patients who missed appointments for more than three consecutive months. Out of the 300, 206 were interviewed using a pre‐structured questionnaire to explore patients’ experiences along with medical record reviews from the patient database. Not feeling sick or not experiencing any symptoms (24.8%) was the major reason why patients did not return to the clinic, followed by far distance from the facility (22.3%). Among other reasons for missing follow‐up appointments, lack of instructions/guidance from the facility (15.3%), acute illness among patients (8.3%), and long waiting time at the facilities (7%) were also documented. Most of these patients (55.4%) continued treatment from other sources, and a majority (54%) preferred private clinics. These results suggest the need for a more patient‐centered care model, including education about hypertension as an asymptomatic but life‐threatening condition and addressing the barrier of travel distance between a patient's home and the health facility. Further, introducing a reminder system using telephone calls, text messages, or home visits by health workers may increase the follow‐up rate among patients.
The effect of medication on the aldosterone‐to‐renin ratio. A critical review of the literature
Authors: Alnazer Rawan M. , Veldhuizen Gregory P. , Kroon Abraham A. , de Leeuw Peter W.
Published: January 2021

The aldosterone‐to‐renin ratio (ARR) is a common screening test for primary aldosteronism in hypertensives. However, patients often use medications that could confound the ARR and, thereby, reduce the interpretability of the test. Since it is not always feasible to stop such medication, several drugs that are supposedly neutral with respect to the ARR have been recommended as alternative treatment. The objective of the present review is to explore whether sufficient evidence exists to justify the recommendations. To this end, we performed a systematic PubMed and Cochrane literature search regarding medications that may influence the ARR. Our review revealed that many commonly prescribed antihypertensives seem to have significant effects on renin, aldosterone, and resulting ARR values. However, the magnitude of these effects is poorly quantifiable with the present level of research. We conclude that several medications can affect the ARR. Not taking this into account could lead to misinterpretation of the ARR. Therefore, standardization of the medications used during ARR measurement is advisable for a reliable and accurate interpretation. Further research is needed to ascertain how to best optimize these medications.
Simultaneous extraction and pasteurization of a drink from “Blood Root” (Justicia secunda) leaves stabilized with a natural preservative: Optimization and storage
Authors: Neba Noveta Binwi , Ngwabie Ngwa Martin , Anuanwen Claris Foncha , Nde Bup Divine
Published: January 2021

Simultaneous extraction and pasteurization (SEPA) has recently been presented as an appealing process in juice processing because of significant reduction in time, energy consumptions, and production cost resulting from the combination of unit operations. However, the optimum SEPA operating conditions and their effects on the quality and shelf‐life of juice are still unmastered. The Doehlert experimental design was used to optimize the SEPA process of juice from Justicia secunda leaves. Optimum conditions for vitamin C retention were temperature (80°C), quantity of ginger (2.6 g/100 ml) and time (20 min) which gave a vitamin C concentration of 4.61 mg/100 ml. The second part of the study evaluated the stability of juice using ginger powder as a natural stabilizer. Results showed that juice produced with and without ginger (WOG) retained 81.27 and 51.18% of their initial vitamin C contents on Day 9 of storage, respectively. Vitamin C content, pH, and acidity showed that addition of ginger preserved the quality of the juice better than that WOG throughout the storage period. Ginger is a natural source of preservative that contributes to the vitamin C content of the juice and extends its shelf‐life from 3 to 9 days for storage at room temperature.

Practical applications

This work describes simple procedures that can be used to extract and pasteurize juice from plant material with simple equipment simultaneously. The optimum conditions that retain more than 90% of the initial vitamin C content of the juice are defined and the use of ginger as a natural preservative that prolongs the shelf‐life of the drink at room temperature makes the process very appealing. The process can be easily adapted and used at both laboratory, local and industrial levels to produce juice of good quality.
Agent‐based simulator of dynamic flood‐people interactions
Authors: Shirvani Mohammad , Kesserwani Georges , Richmond Paul
Published: January 2021

This article presents a simulator for the modelling of the two‐way interactions between flooding and people. The simulator links a hydrodynamic model to a pedestrian model in a single agent‐based modelling platform, Flexible Large‐scale Agent Modelling Environment for the Graphical Processing Unit (FLAMEGPU). Dynamic coupling is achieved by the simultaneous update and exchange of information across multiple agent types. Behavioural rules and states for the pedestrian agents are proposed to account for the pedestrians' presence/actions in/to floodwater. These are based on a commonly used hazard rate (HR) metric to evaluate the risk states of people in floodwater, and by considering two roles for the pedestrians: evacuees or responders for action during or before the flood event, respectively. The potential of the simulator is demonstrated in a case study of a flooded and busy shopping centre for two scenarios: (a) during a flood evacuation and (b) pre‐flood intervention to deploy a sandbag barrier. The evacuation scenario points to changes in floodwater hydrodynamics around congested areas, which either worsen (by 5–8%) or lessen (by 25%) the HR. The intervention scenario demonstrates the utility of the simulator to select an optimal barrier height and number of responders for safe and effective deployment. Accompanying details for software accessibility are provided.
Effects of storage practices on long‐chain polyunsaturated fatty acids and lipid peroxidation of preterm formula milk
Authors: Nessel I. , Khashu M. , Dyall S. C.
Published: January 2021

Background

Preterm formula milk (FM) is often prepared in advance, potentially affecting nutritional quality. Long‐chain polyunsaturated fatty acids (LCPUFAs), important for brain and immune system function, are prone to lipid peroxidation, which correlates with comorbidities of prematurity. The effects of clinical storage practices on LCPUFA content and lipid peroxidation of preterm FM were investigated.

Methods

UK liquid and powder preterm FM (2017) (from two manufacturers) were subjected to routine storage conditions (liquid: refrigeration ≤10 h; powder: weekly preparation in accordance with the manufacturer’s instructions and refrigeration ≤24 h for 4 weeks). LCPUFA content, thiobarbituric acid reactive substances and 4‐hydroxy‐2‐nonenal (HNE) content were analysed.

Results

Storage did not significantly decrease LCPUFA content. The European Society for Paediatric Gastroenterology, Hepatology and Nutrition recommended LCPUFA intake, whereas in utero accretion rates could not be achieved with both FM brands (liquid and powder). Lipid peroxidation was evident on opening, with 6× higher levels in powder. No effect of ≤10‐h refrigeration on peroxidation was seen in liquid FM. In powder FM, it increased over refrigeration (HNE opening: 6.5–9.7 µg mL–1 versus day 28, 24 h: 16.6–36.5 µg mL–1) with a significant interaction between storage time and refrigeration (P = 0.015), with higher HNE at 4 h on days 0, 7, 14 and 21 (all P < 0.05).

Conclusions

The results suggest that preterm FM and storage conditions do not support in utero accretion rates for LCPUFAs. Although the results suggest different susceptibility of liquid and powder FM to peroxidation upon refrigeration, they are too preliminary to make specific recommendations. We suggest minimising storage time of fresh and prepared powder FM, wherever possible.
Effect of glycolic acid, phytic acid, soothing complex containing Emulsion on Hyperpigmentation and skin luminosity: A clinical evaluation
Authors: Houshmand Elizabeth Bahar
Published: January 2021

Background

Improvement in skin luminosity and dyschromia such as postinflammatory hyperpigmentation (PIH) and actinic photodamage are leading causes for cosmetic consultation. Formulation of topical at home treatment is challenging, using a range of modalities, to help hinder or prevent inflammatory mediators without further irritating the skin. Glycolic acid is a known antioxidant; in various free acid levels, it has been introduced as a topical therapy aimed at reducing pigmentation and improving skin texture, tone, and luminosity.

Methods

In a 12‐week clinical study, a novel, topical facial emulsion containing 10% glycolic acid, 2% phytic acid, and soothing complex in emulsion was evaluated for its effectiveness in treating skin quality in American female volunteers with Fitzpatrick skin types II‐VI. Efficacy evaluations were performed at pretreatment baseline, weeks 2, 4, 8, and 12, and included expert clinical grading, and self‐assessment questionnaires. Cutaneous tolerability was also evaluated by assessing subjective and objective irritation of the treatment area.

Results

Significant improvement in the appearance of skin PIH, hyperpigmentation, texture, and tone homogeneity was observed beginning at week 4 and continued through week 12.

Conclusions

The findings suggest that the test product is well suited for at‐home skincare. It was both well‐tolerated and an effective treatment option for addressing hyperpigmentation and overall skin luminosity.
Final‐year undergraduate nursing students’ perceptions of general practice nursing: A qualitative study
Authors: Calma Kaara Ray B. , Halcomb Elizabeth , Williams Anna , McInnes Susan
Published: January 2021

Aim

To explore final‐year nursing students’ perceptions of general practice nursing.

Background

The need for general practice nurses has increased due to growing demands for health care in the community. This demand is exacerbated by a shortage in the general practice nursing workforce. Understanding final‐year nursing students’ perceptions of general practice nursing is important as these may influence career choices.

Design

Qualitative descriptive study within a mixed methods project.

Methods

Telephone interviews were conducted with sixteen final‐year nursing students. Interviews were audio‐recorded, transcribed verbatim and analysed using thematic analysis. Reporting follows the COREQ checklist.

Results

Perceptions of general practice nursing varied between participants and related to three main themes; ways of working; a broad role to meet diverse health needs; and relationships with patients. General practice nurses were seen to have stable and collaborative working relationships, with their role ranging from supporting general practitioners to being autonomous professionals. The nurse's broad role was associated with diverse presentations and was considered interesting and challenging. Participants perceived that general practice nurses had more time to spend with patients, and this helped establish trust, and facilitated patient‐centred care.

Conclusion

Participants’ perceptions of general practice nursing varied, with some students recognising the diversity of the role and others perceiving it as limited. These views were often impacted by others experiences rather than personal experience. These variations underscore the need for students to receive greater exposure to general practice nursing. Review of undergraduate curricula to increase focus on preparing nursing students to work in general practice may help shape students’ interest to seek employment in this setting.

Relevance to clinical practice

Students perceptions of a clinical setting can influence their career decisions. Understanding these perceptions can inform clinicians and managers and highlight areas that may need to be addressed to promote career opportunities.
Nurse‐to‐nurse collaboration between nurses caring for older people in hospital and primary health care: A cross‐sectional study
Authors: Lemetti Terhi , Puukka Pauli , Stolt Minna , Suhonen Riitta
Published: January 2021

Aims and objectives

To assess the level of nurse‐to‐nurse collaboration during the transfer of older people between hospital and primary health care and to evaluate the psychometric properties of the newly developed Nurse‐to‐Nurse Collaboration Between Sectors Instrument.

Background

Nurse‐to‐nurse collaboration is required when older people transfer between hospital and primary health care to enhance the safety and continuity of care to patients. There is a lack of evidence about the nature and level of this collaboration.

Design

A cross‐sectional survey design was used. This study adhered to the STROBE checklist.

Methods

A sample of 443 nurses (university hospital n = 240, primary health care n = 203) participated in the study from October 2017 to June 2018. Nurses completed the Nurse‐to‐Nurse Collaboration Between Sectors Instrument (86 items, 7–point Likert‐type scale), the Nurse‐Nurse Collaboration Scale and the Patient‐Centred Competency Scale.

Results

Nurses rated the overall level of nurse‐to‐nurse collaboration moderately high (mean=4.49, standard deviation=0.83, maximum 7.00). Nurses considered collaboration an important and confidential process, gaining older people's trust in their care. Lower scores were given to the agreement of mutual objectives, policies and guidelines in collaboration, opportunities for job rotation and interacting and networking during the collaboration process. The internal consistency reliability of the newly developed instrument was acceptable.

Conclusions

Nurses collaborate with competence and confidentiality during the transfer of older people between care settings. However, there is a need for more opportunities to collaborate, to obtain mutual agreement about objectives, policies and practices, and better understand other nurse's roles and responsibilities in collaboration. The reliability and validity of the Nurse‐to‐Nurse Collaboration Between Sectors Instrument were acceptable though the number and wording of items will be reviewed and further tested.

Relevance to clinical practice

Nurses need opportunities to collaborate, and there is a need to develop agreed objectives, practices, roles and responsibilities in this collaboration.
Disciplined into good conduct: Gender constructions of users in a municipal psychiatric context in Sweden
Authors: Eivergård Kristina , Enmarker Ingela , Livholts Mona , Aléx Lena , Hellzén Ove
Published: January 2021

Aims and objectives

To examine how gendered discursive norms and notions of masculinity and femininity were (re)produced in professional conversations about users of long‐term municipality psychiatric care. Focus is on the staff's use of language in relation to gender constructions.

Background

Psychiatric care in Sweden has undergone tremendous changes in recent decades from custodian care in large hospitals to a care mainly located in a municipal context. People who need psychiatric care services often live in supporting houses. In municipal psychiatric care, staff conduct weekly professional meetings to discuss daily matters and the users' needs. Official reports of the Swedish government have shown that staff in municipal care services treat disabled women and men differently. Studies exploring gender in relation to users of long‐term psychiatric care in municipalities have problematised the care and how staff, through language, construct users' gender. Therefore, language used by staff is a central tool for ascribing different gender identities of users.

Design

The content of speech derived from audio recordings was analysed using Foucauldian discourse analysis. The COREQ checklist was used in this article.

Results

The results indicate that by relying on gender discourses, staff create a conditional care related to how the users should demonstrate good conduct. In line with that, an overall discourse was created: Disciplined into good conduct. It was underpinned by three discourses inherent therein: The unreliable drinker and the confession, Threatened dignity, and Doing different femininities.

Conclusion

The community psychiatric context generates a discourse of conduct in which staff via spoken language (re)produces gendered patterns and power imbalances as a means to manage daily work routines. Such practices of care, in which constant, nearly panoptic, control despite the intention to promote autonomy, urgently require problematising current definitions of good conduct and normality.
Technique to Fabricate Custom Nasal Pillows and Monoblock Mandibular Advancement Device Using A Digital Workflow for Combination Therapy of Obstructive Sleep Apnea
Authors: Lee Paul T. , Sheridan Ryan R.
Published: January 2021

Combination therapy using continuous positive airway pressure and oral appliance therapy is an effective non‐surgical treatment for obstructive sleep apnea. However, the laboratory expense and additional chairside time prevent it from being a preferred option. This article describes a technique for fabricating custom nasal pillows and monoblock mandibular advancement device with potential lower cost and accelerated timeline using a digital workflow.
Melatonin regulates maternal pancreatic remodeling and B‐cell function during pregnancy and lactation
Authors: Gomes Patricia Rodrigues Lourenço , Vilas‐Boas Eloisa Aparecida , Leite Eduardo de Almeida , Munhoz Ana Cláudia , Lucena Camila Ferraz , Amaral Fernanda Gaspar do , Carpinelli Angelo Rafael , Cipolla‐Neto José
Published: January 2021

The endocrine pancreas of pregnant rats shows evident plasticity, which allows the morphological structures to return to the nonpregnant state right after delivery. Furthermore, it is well‐known the role of melatonin in the maintenance of the endocrine pancreas and its tropism. Studies indicate increasing nocturnal serum concentrations of maternal melatonin during pregnancy in both humans and rodents. The present study investigated the role of melatonin on energy metabolism and in pancreatic function and remodeling during pregnancy and early lactation in rats. The results confirm that the absence of melatonin during pregnancy impairs glucose metabolism. In addition, there is a dysregulation in insulin secretion at various stages of the development of pregnancy and an apparent failure in the glucose‐stimulated insulin secretion during the lactation period, evidencing the role of melatonin on the regulation of insulin secretion. This mechanism seems not to be dependent on the antioxidant effect of melatonin and probably dependent on MT2 receptors. We also observed changes in the mechanisms of death and cell proliferation at the end of pregnancy and beginning of lactation, crucial periods for pancreatic remodeling. The present observations strongly suggest that both functionality and remodeling of the endocrine pancreas are impaired in the absence of melatonin and its adequate replacement, mimicking the physiological increase seen during pregnancy, is able to reverse some of the damage observed. Thus, we conclude that pineal melatonin is important to metabolic adaptation to pregnancy and both the functionality of the beta cells and the remodeling of the pancreas during pregnancy and early lactation, ensuring the return to nonpregnancy conditions.
Molecular evidence for Myripristisjacobus and Scarustaeniopterus new to Bay of Bengal: Sporadic appearance or preliminary colonization?
Authors: Barik Tapan K. , Swain Surya N. , Sahu Bijayalaxmi , Tripathy Bibarani , Acharya Usha R.
Published: January 2021

Individual specimens of Myripristis jacobus Cuvier, 1829 and Scarus taeniopterus Lesson, 1829 were collected from Gopalpur‐on‐sea, Odisha coast, Bay of Bengal. Both the fish samples were assigned species level tags using the conventional taxonomic methods. The capture of both the fish species is of particular interest in that they were new to the Bay of Bengal. Molecular analysis using the mitochondrial cytochrome oxidase subunit I (COI) gene showed high confidence sequence similarity in species identification. The resultant phylogenetic relationships strongly support the monophyly of both the genus with congruent clustering of both the species according to their morphological identification. In addition, the time tree produced is in complete agreement with the recent studies. These studies conclusively prove that both the species might have been originated during the middle to the late Miocene period. Furthermore, both fish species are typical inhabitants of stigmatized coral reefs, confined to the reef regions. These fish species perhaps migrated to the Bengal Bay from the Andaman and Nicobar Islands reef regions because of climatic changes.
Association of depression, pain, resilience, social support with post‐traumatic stress in sexual abuse: A quantile regression approach
Authors: Kim Sunah , Park Suin , Kim Go‐Un
Published: January 2021

Post‐traumatic stress levels and factors influencing the sexual abuse period may differ between victims. This cross‐sectional study conducted a secondary analysis of primary online survey data extracted from a previous study. We examined the extent of trauma (types, timing) and depression, pain, resilience, and social support associated with post‐traumatic stress affecting the post‐traumatic stress percentile. Among 3000 adults aged 19–65 years, 1223 adults experienced childhood sexual abuse, adulthood sexual abuse, or childhood and adulthood sexual abuse. We conducted descriptive statistics, multiple linear regression, and simultaneous quantile regression. Quantile regression analysis showed the 80th percentile groups in childhood sexual abuse, education, depression, and social support were significantly associated with post‐traumatic stress. Depression was significantly and positively associated with post‐traumatic stress. Resilience was significantly and negatively associated with post‐traumatic stress in adulthood sexual abuse victims. Depression and pain were significantly and positively associated with post‐traumatic stress in childhood and adulthood sexual abuse victims. Post‐traumatic stress severity and influencing factors differed according to victims' age when the sexual abuse occurred, implying interventions should be tailored to each victim's post‐traumatic stress level.
Moss stomata do not respond to light and CO2 concentration but facilitate carbon uptake by sporophytes: a gas exchange, stomatal aperture, and 13C‐labelling study
Authors: Kubásek Jiří , Hájek Tomáš , Duckett Jeffrey , Pressel Silvia , Šantrůček Jiří
Published: January 2021

Stomata exert control on fluxes of CO2 and water (H2O) in the majority of vascular plants and thus are pivotal for planetary fluxes of carbon and H2O. However, in mosses, the significance and possible function of the sporophytic stomata are not well understood, hindering understanding of the ancestral function and evolution of these key structures of land plants.

Infrared gas analysis and 13CO2 labelling, with supporting data from gravimetry and optical and scanning electron microscopy, were used to measure CO2 assimilation and water exchange on young, green, ± fully expanded capsules of 11 moss species with a range of stomatal numbers, distributions, and aperture sizes.

Moss sporophytes are effectively homoiohydric. In line with their open fixed apertures, moss stomata, contrary to those in tracheophytes, do not respond to light and CO2 concentration. Whereas the sporophyte cuticle is highly impermeable to gases, stomata are the predominant sites of 13CO2 entry and H2O loss in moss sporophytes, and CO2 assimilation is closely linked to total stomatal surface areas.

Higher photosynthetic autonomy of moss sporophytes, consequent on the presence of numerous stomata, may have been the key to our understanding of evolution of large, gametophyte‐independent sporophytes at the onset of plant terrestrialization.
Effect of Short‐Time High‐Temperature Treatment on the Photosynthetic Performance of Different Heat‐Tolerant Grapevine Cultivars
Authors: Zha Qian , Xi Xiaojun , He Yani , Yin Xiangjing , Jiang Aili
Published: January 2021

To explore the photosynthetic response of short‐term high‐temperature treatments to the leaves of different grape varieties (Shenyue and Shenfeng), we performed 45°C treatments on annual potted grapes in an artificial climate chamber to simulate the summer high‐temperature period. We measured the rapid A‐Ci response curve, 1,5‐ribulose bisphosphate carboxylase/oxygenase (Rubisco) activity and chlorophyll a fluorescence. Photosynthetic performance‐related parameters of grapevine leaves were found to be adversely affected by high temperature; the maximum rates of carboxylation of Rubisco and ribulose diphosphate regeneration and Rubisco activity were all significantly reduced. The JI of the JIP‐test curve disappeared under high‐temperature treatment, and the K peak appeared, indicating that the oxygen‐evolving complex (OEC) had been destroyed. Principal component analysis showed that PSII activity (Fv/Fm, DFABS, φEo, ABS/RC) was greatly affected by high temperature. It was also found that the Rubisco activity and OEC destruction strength were greater in one of the cultivars, and we were able to determine heat resistance based on the phenotype and photosynthetic performance. It can be seen from the above that Shenyue leaves have higher heat tolerance and stronger photosynthetic performance than Shenfeng leaves. This shows that photosynthetic performance is strongly correlated with a grapevine's tolerance to abiotic stress.
Collaboration in Development of New Drugs
Authors: Tian Zhili , Gurnani Haresh , Xu Yi
Published: January 2021

The development of a new drug is costly and uncertain. As such, pharmaceutical firms often collaborate to develop new drugs. We examine the conditions under which firms should collaborate rather than compete in new drug development. We model the collaboration vs. competition decision problem for two firms using a game‐theoretic model and derive the collaboration conditions. Our study demonstrates that development cost and uncertainties in drug treatment efficacy and safety and patient enrollment drive the collaboration or competition decision for firms. We establish conditions based on probabilities of success of drug development, cost rates, and potential market shares under which the firms should collaborate, and show that there exist scenarios under which the firms actually collaborate on the lower efficacy drug. As such, firms need to take into consideration various factors such as the probability of success, the potential market share, and the development cost of each competing drug when determining whether to collaborate or compete in developing new drugs. Finally, we apply our analytical model to illustrate a case study involving collaboration between Bristol‐Myers Squibb and Pfizer.
Redefining the Meaning of Negative History in Times of Sociopolitical Change: A Social Creativity Approach
Authors: Lienen Carmen Sarah , Cohrs J. Christopher
Published: January 2021

This article explores the role negative history plays in political discourse on crisis management and how times of sociopolitical change in turn influence the strategies that can be employed to write a positive historical charter. Choosing Germany as a case study, we analyzed how political leaders negotiate Germany's narrative and political role during the European “refugee crisis” in speeches (n = 332) held between 2015 and 2018. Applying a combination of corpus‐based and qualitative narrative analysis, we found that the context of a crisis is used to attach new meaning to Germany's role in World War II. By focusing on the lessons learned from history and pointing out the parallels between the current crisis and sociopolitical developments that took place 80 years ago, Germany is presented as the ideal advocate for a free and united Europe, a narrative that legitimizes its advancingly dominant role within the EU and beyond. The analysis demonstrates how times of change can facilitate social creativity strategies for nations whose past is dominated by negative history, with implications for the theory of identity management.
Analysis of sticky generative cell mutants reveals that suppression of callose deposition in the generative cell is necessary for generative cell internalization and differentiation in Arabidopsis
Authors: Oh Sung‐Aeong , Park Hyo‐Jin , Kim Myung‐Hee , Park Soon‐Ki
Published: January 2021

In flowering plants, double fertilization between male and female gametophytes, which are separated by distance, largely depends on the unique pattern of the male gametophyte (pollen): two non‐motile sperm cells suspended within a tube‐producing vegetative cell. A morphological screen to elucidate the genetic control governing the strategic patterning of pollen has led to the isolation of a sticky generative cell (sgc) mutant that dehisces abnormal pollen with the generative cell immobilized at the pollen wall. Analyses revealed that the sgc mutation is specifically detrimental to pollen development, causing ectopic callose deposition that impedes the timely internalization and differentiation of the generative cell. We found that the SGC gene encodes the highly conserved domain of unknown function 707 (DUF707) gene that is broadly expressed but is germline specific during pollen development. Additionally, transgenic plants co‐expressing fluorescently fused SGC protein and known organelle markers showed that SGC localizes in the endoplasmic reticulum, Golgi apparatus and vacuoles in pollen. A yeast two‐hybrid screen with an SGC bait identified a thaumatin‐like protein that we named GCTLP1, some homologs of which bind and/or digest β‐1,3‐glucans, the main constituent of callose. GCTLP1 is expressed in a germline‐specific manner and colocalizes with SGC during pollen development, indicating that GCTLP1 is a putative SGC interactor. Collectively, our results show that SGC suppresses callose deposition in the nascent generative cell, thereby allowing the generative cell to fully internalize into the vegetative cell and correctly differentiate as the germline progenitor, with the potential involvement of the GCTLP1 protein, during pollen development in Arabidopsis.
Clinical recovery of 5 dogs from amatoxin mushroom poisoning using an adapted Santa Cruz protocol for people
Authors: Goupil Ryan C. , Davis Megan , Kaufman Abigail , Roberts Diane , Mitchell Todd
Published: January 2021

Objective

To describe the clinical course, treatment, and outcome of 5 dogs following ingestion of toxic Amanita spp. mushrooms containing amatoxins using an adapted version of the Santa Cruz protocol developed for people.

Case series summary

Five dogs were presented with clinical signs compatible with amanitin toxicity with witnessed ingestion noted in 3 of 5 dogs. Clinical findings included acute onset vomiting and diarrhea, lethargy, and hepatopathy including signs of fulminant hepatic failure (increased liver enzyme activities, hyperbilirubinemia, prolonged clotting times, and hypoglycemia were noted among these cases). Urine toxicological screening confirmed the presence of Amanita toxins in 4 cases with expert mycologist speciation in the fifth. Core interventions included percutaneous biliary drainage, use of octreotide, and early nil per os orders. All dogs survived to discharge with this treatment strategy.

New or unique information provided

This case series describes the use of a modified version of the Santa Cruz protocol to address amatoxin‐induced fulminant hepatic failure in dogs. The protocol was safe, well tolerated, and all patients made a full clinical recovery.
Performance and Manufacturing of Silicon-Based Vapor Chambers
Authors: Liu Tanya , Asheghi Mehdi , Goodson Kenneth E.
Published: January 2021

This paper reviews recent progress in the development of silicon-based vapor chambers for heat spreading in electronic packages. Effective hotspot mitigation is an increasingly challenging issue in electronics thermal management, and the use of silicon vapor chambers creates opportunities for thermal-expansion matched, high performance heat spreaders that can be directly integrated with the semiconductor die. While silicon microheat pipes have been extensively studied as one-dimensional heat transport mechanisms for heat routing in semiconductor substrates, silicon vapor chambers require special consideration and different manufacturing approaches due to the different heat transport configurations involved. The following review therefore provides an overview on the evolution of silicon vapor chambers in terms of fabrication strategies and performance characterization. Particular focus is given to opportunities and challenges associated with using silicon as the vapor chamber envelope material rather than more traditional metal-based vapor chambers, such as the ability to optimize the wick geometry with greater fidelity and issues with manufacturing scalability.
Carbapenem Use Is Driving the Evolution of Imipenemase 1 Variants
Authors: Cheng Zishuo , Bethel Christopher R. , Thomas Pei W. , Shurina Ben A. , Alao John-Paul , Thomas Caitlyn A. , Yang Kundi , Marshall Steven H. , Zhang Huan , Sturgill Aidan M. , Kravats Andrea N. , Page Richard C. , Fast Walter , Bonomo Robert A. , Crowder Michael W.
Published: January 2021

Metallo-β-lactamases (MBLs) are a growing clinical threat because they inactivate nearly all β-lactam-containing antibiotics, and there are no clinically available inhibitors. A significant number of variants have already emerged for each MBL subfamily.
Electrostatic-Mediated Affinity Tuning of Lysostaphin Accelerates Bacterial Lysis Kinetics and Enhances
In Vivo
Efficacy
Authors: Zhao Hongliang , Eszterhas Susan , Furlon Jacob , Cheng Hao , Griswold Karl E.
Published: January 2021

Drug-resistant bacterial pathogens are a serious threat to global health, and antibacterial lysins are at the forefront of innovative treatments for these life-threatening infections. While lysins’ general mechanism of action is well understood, the design principles that might enable engineering of performance-enhanced variants are still being formulated.
De Novo
Cobalamin Biosynthesis, Transport, and Assimilation and Cobalamin-Mediated Regulation of Methionine Biosynthesis in Mycobacterium smegmatis
Authors: Kipkorir Terry , Mashabela Gabriel T. , de Wet Timothy J. , Koch Anastasia , Dawes Stephanie S. , Wiesner Lubbe , Mizrahi Valerie , Warner Digby F.
Published: January 2021

Alterations in cobalamin-dependent metabolism have marked the evolution of
Mycobacterium tuberculosis
into a human pathogen. However, the role(s) of cobalamin in mycobacterial physiology remain poorly understood.
CRNKL1 Is a Highly Selective Regulator of Intron-Retaining HIV-1 and Cellular mRNAs
Authors: Xiao Han , Wyler Emanuel , Milek Miha , Grewe Bastian , Kirchner Philipp , Ekici Arif , Silva Ana Beatriz Oliveira Villela , Jungnickl Doris , Full Florian , Thomas Marco , Landthaler Markus , Ensser Armin , Überla Klaus
Published: January 2021

To regulate its complex splicing pattern, HIV-1 uses the adaptor protein Rev to shuttle unspliced or partially spliced mRNA from the nucleus to the cytoplasm. In the absence of Rev, these RNAs are retained in the nucleus, but it is unclear why.
Atypical Divergence of SARS-CoV-2 Orf8 from Orf7a within the Coronavirus Lineage Suggests Potential Stealthy Viral Strategies in Immune Evasion
Authors: Neches Russell Y. , Kyrpides Nikos C. , Ouzounis Christos A.
Published: January 2021

Orf8 is one of the most puzzling genes in the SARS lineage of coronaviruses, including SARS-CoV-2. Using sophisticated sequence comparisons, we confirm its origins from Orf7a, another gene in the lineage that appears as more conserved, compared to Orf8.
Comparative Genomic Analysis of
Mycobacteriaceae
Reveals Horizontal Gene Transfer-Mediated Evolution of the CRISPR-Cas System in the Mycobacterium tuberculosis Complex
Authors: Singh Anoop , Gaur Mohita , Sharma Vishal , Khanna Palak , Bothra Ankur , Bhaduri Asani , Mondal Anupam Kumar , Dash Debasis , Singh Yogendra , Misra Richa
Published: January 2021

Comparative genomic analysis of prokaryotes has led to a better understanding of the biology of several pathogenic microorganisms. One such clinically important pathogen is
M. tuberculosis
, the leading cause of bacterial infection worldwide.
Caught between Two Genes: Accounting for Operonic Gene Structure Improves Prokaryotic RNA Sequencing Quantification
Authors: Reiter Taylor
Published: January 2021

RNA sequencing (RNA-seq) has matured into a reliable and low-cost assay for transcriptome profiling and has been deployed across a range of systems. The computational tool space for the analysis of RNA-seq data has kept pace with advances in sequencing.
Morphine or hydromorphone: which should be preferred? A systematic review
Authors: Spénard Sarah , Gélinas Charles , D. Trottier Evelyne , Tremblay-Racine Fannie , Kleiber Niina
Published: January 2021

Objective

To systematically review available paediatric literature on comparisons between morphine (Mo) and hydromorphone (Hm), to guide clinicians to rationally use these medications.

Design

Systematic review within four databases for all studies published from 1963 to July 2019.

Setting

All paediatric settings.

Eligibility

All studies comparing Mo to Hm in individuals younger than 21 years.

Main outcome measures

The primary outcome was to compare clinical efficacy and side effects of Mo and Hm. The secondary outcomes were the comparison of pharmacokinetic profiles and the description of predefined Mo to Hm conversion ratios used across the paediatric literature.

Results

Among 754 abstracts reviewed, 59 full-text articles met inclusion criteria and 24 studies were included in the analysis: 4 studies compared pharmacodynamics of Mo and Hm and 20 studies reported the use of a predefined Mo to Hm conversion ratio. Most studies had a poor methodological quality. Available evidence suggests that, when given intravenously, the equianalgesic ratio of Mo to Hm is 5:1. Intravenous administration with this ratio results in a similar rate of adverse effects, including pruritus and nausea. The epidural administration with a ratio of 10:1 results in more pruritus and urinary retention with Mo than Hm. Pharmacokinetic data were reported in only one study. A wide range of pre-established ratios for different routes of administration were reported, but few were based on evidence.

Conclusion

Current literature does not permit a rational choice between Mo and Hm. A ratio of 5:1 seems adequate for intravenous administration and leads to a similar rate of adverse effects.