bluuebunny/crossref_metadata_2025 huggingface dataset:
Does Keloid Histology Influence Recurrence?
Authors: Nangole Ferdinand W. , Ouyang Kelsey , Anzala Omu , Ogeng'o Julius , Agak George W. , Zuriel Daniel
Published: January 2021

Keloids are fibroproliferative disorders characterized by high recurrence rates, with few factors known to influence the same. We conducted a study to determine whether keloid histology influences recurrence. This was a prospective longitudinal study to determine whether histopathological parameters of keloid influence recurrence. Patients with keloids managed by surgical excision were followed up at Kenyatta National Hospital between August 2018 and July 2020. The excised keloids were processed for histology using hematoxylin,/eosin, Masson, and trichrome stains. The slides were analyzed for inflammatory cells, fibroblasts, and capillary density using the hot spot technique and correlated to keloid recurrence. Postoperative follow-up was for a minimum of 1 year. A total of 90 patients with 104 keloids were recruited in the study. Overall keloid recurrence rate was 28.6%. There was a correlation between the absolute count of more than 50 per High power field of lymphocytes, fibroblasts, and macrophages with recurrence of the disease. The sensitivity and specificity for the above parameters were lymphocytes 48% and 81%, macrophages 57% and 83%, mast cells 32% and 33%, and fibroblasts 41% and 91%, respectively. There was no correlation between mast cells and vascularity status with recurrence. Routine histology should, therefore, be performed to determine these parameters. Close monitoring and second-line therapy should be considered for patients with elevated macrophages and/or lymphocytes so as to reduce the risk of recurrence.
Access to assisted reproduction in Latin America: recent trends and future perspectives
Authors: Horton Marcos
Published: January 2021

Assisted Reproduction is now an established technology to treat infertility. New technological and biomedical advances, added to changing sociocultural views in modern societies have broaden the scope of Assisted Reproduction Treatment, so prospective parents today include conventional infertility couples, single women, or men, gay/lesbian individuals, HIV serodiscordant couples, or carriers of genetic conditions. In addition, younger patients can decide on gamete storage for later use, due to medical or social reasons. The situation in Latin America varies significantly in different countries, despite sharing a common cultural and religious background, but those countries with recent sanctions of IVF laws, regulations, or other legislation related to civil rights, gender identity, or same sex marriage show better access of its population to Assisted Reproduction Treatment.
Expected numbers of embryos to transfer in in vitro fertilization: what affects?
Authors: Cui Linlin , Liu Yizhou , Meng Yueru , Zhang Bingqian , Tang Rong , Chen Zi-Jiang
Published: January 2021

Introduction:

Increased multiple pregnancy rate and resultant complications are some of the greatest concerns for in vitro fertilization (IVF) due to the practice of multiple embryo transfer. Although in some countries elective single embryo transfer has already been mandatory, in majority of other countries, clinical counsel still plays very important role to affect expected number of embryos transferred (ENET). Here we aim to explore the impact factors for ENET of IVF patients in order to provide scientific suggestions for clinical counsel before ET.

Methods:

We performed a survey of impact factors on ENET using a self-designed questionnaire in a total of 1154 IVF couples. Questions about policy change, medical concerns, and social-cultural information were included.

Results:

When the policy for restriction of family size was lifted, the percentages for double embryos transferred (77.8% vs. 63.7%) and multiple embryos transferred (8.0% vs. 3.9%) decreased significantly, while more tended to choose single embryo transfer (SET) (14.2% vs. 32.4%, P<0.01). Patients of more advanced age were more likely to choose SET (12.9% for 18–24 y, 11.8% for 25–29 y, 12.0% for 30–34 y, 22.4% for 35–39 y, and 28.6% for over 40 y, P=0.01). More subjects with previous labor preferred SET than those without (23.3% vs. 12.4%, P<0.01). In addition, the proportion of SET choice was significantly decreased with infertility duration prolonged (1 vs. 2 y vs. 3 vs. ≥4 y: 24.2% vs. 14.9% vs. 11.1% vs. 11.2%, P<0.01). On the basis of further investigation for reasons of ENET, specific formula including individual weighted policy, medical, and social-cultural factors was derived.

Conclusions:

Collectively, ENET for IVF patients is a complex, multi-factorial decision. The heterogeneity between patients due to differential policy restriction, medical concerns, and social-cultural background should be fully considered in clinical counsel about ENET.
Application of holistic medicine in the field of reproductive medicine: is it right to only focus on cells and organs? It is a time to convert to a new paradigm in reproductive medicine
Authors: Morimoto Yoshiharu , Ida Mamoru , Inoue Tomoko , Fukuda Aisaku
Published: January 2021

About 40 years progress of artificial reproductive technology made dream of many patients come true. However, there still remain many patients with recurrent failures of IVF by the conventional technologies. It is because we have too much focused on cells such as oocyte and sperm, and organs such as uterus, ovary, and testis. It is a time to convert to new paradigm in reproductive medicine. We should treat the whole body that includes mind and whole body. Integrated medicine considering nutrition, mental care, and other alternative medicine should be applied to raise success in artificial reproductive technology. If we can collect high quality evidence from the field, it would open the window for new era and solve issues that cannot be treated via conventional western technologies.
Exploring the prevalence of high-risk obstetric conditions diagnosed by point-of-care ultrasound evaluation in a rural Ugandan population: a cohort study
Authors: Dougherty Anne , Kasten Miriam , McDonald Maureen , Angela Njeri , Kawooya Michael , Matovu Alphonsus , Destigter Kristen
Published: January 2021

Objective:

The aim of this study was to determine the prevalence of high-risk obstetric conditions identified by point-of-care ultrasound in a rural Ugandan community and compare them with known rates in high-income settings.

Methods:

Pregnant women in a rural Ugandan clinic were offered a screening obstetric ultrasound at a late second or third trimester antenatal visit (Clearvue 350). Appropriate follow-up was determined by a preset algorithm. Placental abnormalities, multiple gestations, and fetal malpresentation were recorded. Descriptive statistics were used for analysis.

Results:

Fetal malpresentation in the third trimester was found in 15% [confidence interval (CI), 11.7–18.6] of pregnancies. Rates of multiple gestations and placental location abnormalities were 4% (CI, 2.7–5.2) and 1.7% (CI, 0.8–2.5), respectively. Overall, prevalence of abnormal placentation was comparable to published rates, although persistent fetal malpresentation was higher than in the United States. The rate of multiple gestations is on par with United States data despite lack of access to artificial reproductive technology.

Conclusions:

Given that placental abnormalities, multiple gestations, and fetal malpresentation in a rural Ugandan population are at least as common as in high-income countries, and emergency obstetric care is more difficult to access in Uganda, the contribution of these conditions to maternal mortality is likely higher in rural Uganda. Ultrasound can be used to identify and refer patients to higher-level facilities for safe delivery.
SMALL-GAUGE TECHNIQUES FOR REMOVING A FLUOCINOLONE ACETONIDE IMPLANT
Authors: Knight Darren K. , Wang Angeline L. , Tsao Sean W. , Carter Steven L. , Mehta Mitul C.
Published: January 2021

Purpose:

Long-acting injectable fluocinolone releasing implants are used in clinical practice. Although limited in scope, situations may arise where removal of the implant is warranted. We set out to describe possible explantation techniques and to determine whether these implants can be safely removed from a standard sclerotomy or eliminated using a vitrectomy system.

Methods:

A vitreoretinal surgery system was designed using a porcine eye model. A fluocinolone implant was injected into the vitreous cavity. Pars plana vitrectomy was performed and the vitreous cavity was infused with balanced salt solution. The injected implants were removed from 23-Gauge (G) and 25-Gauge (G) vitrectomy cannulas with 27-G forceps. The implants were examined under the microscope for induced defects. Implants were injected into the eye model and eliminated using a 23-G and 25-G vitrector system.

Results:

The implant was removed from both the 23-G and 25-G vitrectomy cannulas with only mild structural damage to the implant. During implant extraction through the 25-G sclerotomy, the cannula was dislodged from the incision along with the implant. The most technically challenging portion involved aligning the implant coaxially to allow for removal en bloc through the sclerotomy site. Implants could be eliminated using both the 23-G and 25-G vitrector using a low-cut rate.

Conclusion:

The fluocinolone implant was removed safely via standard 23-G or 25-G vitrectomy systems. It is unknown whether intraocular manipulation will affect pharmacokinetics of drug delivery if the implant is not explanted.
Early-onset Exfoliation Syndrome: A Literature Synthesis
Authors: Mayro Eileen L. , Ritch Robert , Pasquale Louis R.
Published: January 2021

Precis:

We conducted a literature review of younger patients with exfoliation syndrome (XFS) in an attempt to identify case similarities and better understand disease etiology.

Purpose:

XFS that predisposes to secondary glaucoma is a strongly age-related condition. We performed a literature review of XFS and exfoliation glaucoma (XFG) in patients aged younger than 40 years to examine potential common characteristics and gain clues to its etiology.

Methods:

We conducted a broad literature search with appropriate keywords and manually extracted key demographic and ocular features on younger XFS and XFG cases. Articles that did not provide past ocular history on early-onset XFS/XFG were excluded.

Results:

We identified 12 cases of XFS and XFG in patients from 13 to 40 years old (8 females; 11 White; 5 from Iran). All had past ocular history remarkable for intraocular surgery for other glaucoma conditions (7 cases), other ocular diseases (3 cases), or ocular trauma (2 cases).

Conclusions:

All reported early-onset XFS and XFG cases arise in the setting of events that produced a significant disruption of the blood-aqueous barrier. Understanding the metabolic alterations of aqueous humor from such cases could provide clues regarding how exfoliation material forms.
Axillary Botulinum Toxin Injection for the Treatment of Moderate to Severe Hyperhidrosis
Authors: Baghchechi Mohsen , Macknet Kenneth D. , Jacob Sharon E.
Published: January 2021

Primary focal hyperhidrosis can cause lifelong distress in everyday activities. Some patients cannot adequately decrease excessive perspiration with over-the-counter or prescription-strength antiperspirants. Oral glycopyrrolate is an anticholinergic medication that can decrease perspiration but may also lead to intolerable systemic side effects. Botulinum toxin injected into the axilla provides immediate symptomatic relief that lasts for approximately 6 months. Offering patients botulinum toxin as a second-line agent for treatment-resistant axillary hyperhidrosis can markedly improve quality of life with minimal side effects.
Self-Regulated Learning On Program Entry in Doctor of Physical Therapy Students: A Pilot Study
Authors: Martin Jennifer G. , Smith Nancy S. , Wendt Chris
Published: January 2021

Introduction.

The transition to graduate study can be difficult for entry-level physical therapist (Doctor of Physical Therapy [DPT]) students to make. One factor that may support this transition is the development of self-regulated learning (SRL). SRL has been associated with academic success in graduate health professions programs. Despite previous academic achievement, some DPT students struggle with first semester coursework. It is unknown whether these students have adequate SRL skills. Therefore, this study examined students' perceived SRL skills on program entry.

Methods.

Participants enrolled in their first semester of a DPT program were recruited from a medium-sized historically minority serving institution in the Southeastern United States. Doctor of Physical Therapy students (N = 28) completed the Learning and Study Strategies Inventory (LASSI) instrument to discover perceived abilities in SRL. The LASSI is a valid and reliable instrument that assesses skills, strategies, and behaviors of SRL and has been used in other graduate health professions. Demographic data and LASSI scores were evaluated using descriptive statistics, and between-group comparisons were performed using nonparametric independent tests and analysis of variance. Significance was set at an alpha level of <.05.

Results.

Entering students perceived a need for moderate or high levels of support in most areas of SRL as measured by the LASSI. Statistically significant demographic differences in scale scores found within the cohort included minority status, undergraduate institution, and gender.

Discussion/Conclusion.

This study provides insights into the areas of support DPT students need for SRL that may have implications for early academic support. Diverse students may have different supportive needs. Further research is needed to discover SRL development needs in DPT students.
Crimean-Congo hemorrhagic fever virus vaccine: past, present, and future
Authors: Behboudi Emad , Kakavandi Ehsan , Hamidi-Sofiani Vahideh , Ebrahimian Arefeh , Shayestehpour Mohammad
Published: January 2021

Crimean-Congo hemorrhagic fever (CCHF) has been recognized as a tick-borne infection caused by a member of the Nairoviridae family within the Bunyavirales order, named CCHF virus. CCHF virus is a zoonotic virus, so transferred between vertebrates and humans. Therefore, vaccination in humans and animals might reduce the risk of infection. Currently, there are no globally licensed vaccines or therapeutics for CCHF. Although several studies have been performed on the production of the CCHF vaccine, any of these vaccines were not fully protective. Hence, the development of a new generation of vaccines could contribute to better management of CCHF. In this review, we will discuss on features of these vaccine candidates.
Navigator-Guided Motion and B0 Correction of T2*-Weighted Magnetic Resonance Imaging Improves Multiple Sclerosis Cortical Lesion Detection
Authors: Liu Jiaen , Beck Erin S. , Filippini Stefano , van Gelderen Peter , de Zwart Jacco A. , Norato Gina , Sati Pascal , Al-Louzi Omar , Kolb Hadar , Donadieu Maxime , Morrison Mark , Duyn Jeff H. , Reich Daniel S.
Published: January 2021

Background

Cortical lesions are common in multiple sclerosis (MS). T2*-weighted (T2*w) imaging at 7 T is relatively sensitive for cortical lesions, but quality is often compromised by motion and main magnetic field (B0) fluctuations.

Purpose

The aim of this study was to determine whether motion and B0 correction with a navigator-guided gradient-recalled echo sequence can improve cortical lesion detection in T2*w magnetic resonance imaging.

Materials and Methods

In this prospective study, a gradient-recalled echo sequence incorporating a navigator allowing for motion and B0 field correction was applied to collect T2*w images at 7 T from adults with MS between August 2019 and March 2020. T2*-weighted images were acquired in 1 to 3 partially overlapping scans per individual and were reconstructed using global average B0 correction (“uncorrected”) or motion correction and spatially linear B0 correction (“corrected”). Image quality rating and manual segmentation of cortical lesions were performed on uncorrected and corrected images. Lesions seen on a single scan were retrospectively evaluated on the complementary scan. The association of cortical lesions with clinical disability was assessed. Mixed models were used to determine the effect of correction on lesion detection as well as on the relationship between disability and lesion count.

Results

A total of 22 T2*w scans were performed on 11 adults with MS (mean [SD] age, 49 [11] years; 8 women). Quality improved for 20 of 22 scans (91%) after correction. A total of 69 cortical lesions were identified on uncorrected images (median per scan, 2; range, 0–11) versus 148 on corrected images (median per scan, 4.5; range, 0–25; rate ratio [RR], 2.1; P < 0.0001). For low-quality uncorrected scans with moderate to severe motion artifact (18/22, 82%), there was an improvement in cortical lesion detection with correction (RR, 2.5; P < 0.0001), whereas there was no significant change in cortical lesion detection for high-quality scans (RR, 1.3; P = 0.43).

Conclusions

Navigator-guided motion and B0 correction substantially improves the overall image quality of T2*w magnetic resonance imaging at 7 T and increases its sensitivity for cortical lesions.
Morphological Boundaries of the Parotid Gland in Koreans
Authors: Kim Ye-Gyung , Jeon Anna , Sui Hong-Jin , Hwang Kun , Han Seung-Ho
Published: January 2021

This study aimed to examine the accurate location and boundary of the parotid gland in Koreans.

Forty hemifaces from embalmed cadavers (mean age: 73 years) were studied. The line connecting the porion, gonion, and gnathion was used as a reference line. To measure the boundary of the parotid gland, the Frankfort horizontal line was used as thex-axis, whereas the vertical line passing through the porion was used as they-axis. All measurements were taken from the lateral side of the face.

The parotid gland has a variety of shapes: irregular, reverse triangle, and falciform. In all specimens, the boundary of the parotid gland was located 20 to 60 mm below the Frankfort horizontal line and located 10 mm anterior to they-axis. On average, the most anterior and posterior distances of the parotid gland from the porion-gonion line were 36.4 ± 13.9 mm and 20.1 ± 10.5 mm, respectively, and the most inferior distance of the parotid gland from the gonion-gnathion line was 9.8 ± 5.8 mm. All specimens of parotid glands were found within an area 20 to 40 mm below the Frankfort horizontal line and 10 mm to the left of they-axis. The most anterior point of the parotid gland was observed at varying locations. The maximum value of the most anterior point was 61.26 mm; it rarely exceeded the ectocanthion. The most posterior points of the parotid gland were located between the mastoid process and sternocleidomastoid muscle.

These results might be useful for preventing injury to the parotid gland during facial rejuvenation procedures.
Frontal Sinus Fractures: 10-Year Contemporary Experience at a Level 1 Urban Trauma Center
Authors: Obayemi Adetokunbo , Losenegger Tasher , Long Sallie , Spielman Daniel , Casiano Michael F. , Reeve Gwendolyn , Kacker Ashutosh , Stewart Michael , Sclafani Anthony
Published: January 2021

Frontal sinus fractures account for 5% to 15% of all facial fractures, and have traditionally been associated with high kinetic energy blunt injury. Surgical management is largely focused on minimizing potentially serious sequelae including frontal sinus dysfunction, CSF leak, and significant cosmetic deformity. An institutional database of 1944 patients presenting with maxillofacial fractures over a 10-year period was queried. Demographics, mechanism of injury, yearly trends, surgical approaches, and follow-up data were examined. A total of 160 (8.3%) patients presented with at least 1 fracture of the frontal sinus anterior table, posterior table, or frontal sinus outflow tract during the study period. The average annual number of cases was 15.9 ± 5.7 per year with a peak of 21.5 ± 4.0 cases during the 2014 to 2015 period and a decline to 8.5 ± 1.5 cases/year from 2016 to 2017. Among those patients with falls, 61.5% (n = 40) were a result of tripping or fainting at a height of <6 ft. 55.6% of fracture types were isolated to the anterior table, but fracture location was not significantly associated with operative intervention. Cases of operative fracture type had a higher rate of both displacement and comminution compared to nonoperative fractures (P < 0.00001). Of all patients presenting with frontal sinus fractures, 75% of cases were managed nonoperatively. However, many patients presented with falls and other seemingly low energy injuries which are not traditionally associated with frontal sinus trauma. These results highlight the need for continued follow-up even in otherwise low-risk urban populations in order to avoid long term sinus dysfunction.
Fronto-Orbital Advancement and Posterior Cranial Vault Expansion Using Distraction Osteogenesis in Patients With Multiple Craniosynostosis
Authors: Kamil Muhammad , Oyoshi Tatsuki , Komasaku Soichiro , Kuroki Shinichi , Higa Nayuta , Yoshimoto Koji
Published: January 2021

This study aimed to evaluate the treatment outcomes and the efficiency of techniques of fronto-orbital advancement (FOA) and posterior cranial vault expansion (PCVE) using distraction osteogenesis in patients with multiple craniosynostosis. We assessed the treatment results and outcomes of 8 patients with multiple craniosynostosis at the Kagoshima University Hospital between 2005 and 2019. Each 4 patients underwent FOA and PCVE, respectively, using distraction osteogenesis. The cranial volume and developmental quotient (DQ) were measured at the preoperative period and 1 year after surgery. The mean patient age at surgery was 22 months. The mean preoperative cranial volume was 1027 and 1071 cm3 in the FOA and PCVE groups, respectively. The mean preoperative DQ scores were 74 and 67, respectively. After 1-year of follow-up, the corresponding mean cranial volume became 1108 and 1243 cm3, respectively. The corresponding mean DQ scores also improved to 74 and 81, respectively. The postoperative follow-ups in all cases were uneventful, except for persistent epilepsy in 1 patient. Fronto-orbital advancement and PCVE using distraction osteogenesis might contribute to good outcomes in expanding cranial volume, cosmetic osteogenesis, and infantile development in patients with multiple craniosynostosis. Regarding the cranial volume expansion, especially, PCVE using distraction osteogenesis is more effective than FOA.
Overlooked Piece of Wood Served as a Vector Transmitting Clostridium Perfringens: A Case Report Emphasizing the Awareness of Gas-Forming Organisms in Posttraumatic Pneumocephalus
Authors: Andereggen Lukas , Beck Juergen
Published: January 2021

The radiological depiction of posttraumatic pneumocephalus is due to trapped air in most cases. Although rarely reported, it can also be the result of a gas-forming organism, requiring immediate treatment due to high mortality. Here, we report on an elderly patient with radiological appearance of posttraumatic intracranial pneumocephalus after a wound was closed without recognition of a retained tree branch. The piece of wood served as a vector for transmission of Clostridium perfringens causing the collection of abnormal intracranial air. Radical excision of temporal muscle tissue along with extensive evacuation of the brain abscess and targeted intravenous antibiotics resulted in minor morbidity.

Although a piece of wood can easily be missed with current diagnostic imaging, it is crucial that both clinicians and radiologists are aware of the presence of air and its differential diagnosis in posttraumatic pneumocephalus, in order to allow timely treatment in this fatal disease.
Is Le Fort I Distraction Enough to Treat Severe Midface Hypoplasia?
Authors: Goel Pedram , Fahradyan Artur , Wolfswinkel Erik M. , Jacob Laya , Yen Stephen L-K. , Urata Mark M. , Hammoudeh Jeffrey A.
Published: January 2021

Background:

In severe cases of maxillary hypoplasia, Le Fort I distraction may be required for treatment. This study describes our experience with internal distraction devices and assesses our outcomes in patients with a negative overjet on average >15 mm.

Methods:

A retrospective review of patients with a history of cleft lip and/or palate who underwent Le Fort I distraction at our institution from 11/2007-11/2017 was performed. Data regarding demographics, procedural details and outcomes were collected and analyzed.

Results:

Twenty patients, 13 (65.0%) male and 7 (30.0%) female, were included. All (100%) patients had a history of cleft lip and/or palate and 2 (10.0%) of them had associated syndromes. All 20 patients underwent internal distraction. The average age at surgery was 17.8 years (range 15.2–20.7, SD 1.6 years). The average preoperative negative overjet was 19.27 mm (range 10–30, SD 5.63 mm). The mean total distraction length was 15.3 mm (range 0–30, SD 6.72 mm). There were no intraoperative complications, however, there were a total of 4 (20.0%) postoperative complications, 2 of which required reoperation due to device malfunction or displacement. 14 (70.0%) patients had repeat procedures to complete occlusal correction or correct relapse.

Conclusions:

Maxillary distraction alone was insufficient for correction of maxillary discrepancies averaging >15 mm. Instead, it's utility may be in positioning the maxilla for a more viable final advancement and fixation procedure, rather than being solely responsible for achieving normal occlusion during distraction.
Magnitude, change over time, demographic characteristics and geographic distribution of excess deaths among nursing home residents during the first wave of COVID-19 in France: a nationwide cohort study
Authors: Canouï-Poitrine Florence , Rachas Antoine , Thomas Martine , Carcaillon-Bentata Laure , Fontaine Roméo , Gavazzi Gaëtan , Laurent Marie , Robine Jean-Marie
Published: January 2021

Importance

Nursing home (NH) residents are particularly vulnerable to SARS-CoV-2 infections and coronavirus disease 2019 (COVID-19) lethality. However, excess deaths in this population have rarely been documented.

Objectives

The primary objective was to assess the number of excess deaths among NH residents during the first wave of the COVID-19 pandemic in France. The secondary objectives were to determine the number of excess deaths as a proportion of the total excess deaths in the general population and determine whether a harvesting effect was present.

Design

We studied a cohort of 494,753 adults (as of March 1st, 2020) aged 60 and over in 6,515 NHs in mainland France. This cohort was exposed to the first wave of the COVID-19 pandemic (from March 1st to May 31st, 2020) and was compared with the corresponding, reference cohorts from 2014 to 2019 (using data from the French National Health Data System).

Main outcome and measures

The main outcome was all-cause death. Weekly excess deaths and standardized mortality ratios (SMRs) were estimated.

Result

There were 13,505 excess deaths among NH residents. Mortality increased by 43% (SMR: 1.43). The mortality excess was higher among males than among females (SMR: 1.51 and 1.38, respectively) and decreased with age (SMRs in females: 1.61 in the 60-74 age group, 1.58 for 75-84, 1.41 for 85-94, and 1.31 for 95 or over; Males: SMRs: 1.59 for 60-74, 1.69 for 75-84, 1.47 for 85-94, and 1.41 for 95 or over). We did not observe a harvesting effect (up until August 30th, 2020). By extrapolating to all NH residents nationally (N=570,003), the latter accounted for 51% of the total excess deaths in the general population (N=15,114 out of 29,563).

Conclusion

NH residents accounted for about half of the total excess deaths in France during the first wave of the COVID-19 pandemic. The excess death rate was higher among males than females and among younger residents than among older residents. We did not observe a harvesting effect. A real-time mortality surveillance system and the identification of individual and environmental risk factors might help to design the future model of care for older dependent adults.

Key points

During the first wave of the COVID-19 pandemic in France, the mortality among nursing home residents increased by 43%.

Nursing home residents accounted for 51% of the total excess deaths in France.

The excess mortality was higher among younger residents than among older residents.

The excess mortality was higher among males than among females.

We did not observe a harvesting effect during the study period (ending on August 30th, 2020, i.e., three months after the end of the first wave).
Model-based cellular kinetic analysis of SARS-CoV-2 infection: different immune response modes and treatment strategies
Authors: Zhou Zhengqing , Zhao Ziheng , Shi Shuyu , Wu Jianghua , Li Dianjie , Li Jianwei , Zhang Jingpeng , Gui Ke , Zhang Yu , Mei Heng , Hu Yu , Ouyang Qi , Li Fangting
Published: January 2021

Increasing number in global COVID-19 cases demands for mathematical model to analyze the interaction between the virus dynamics and the response of innate and adaptive immunity. Here, based on the assumption of a weak and delayed response of the innate and adaptive immunity in SARS-CoV-2 infection, we constructed a mathematical model to describe the dynamic processes of immune system. Integrating theoretical results with clinical COVID-19 patients’ data, we classified the COVID-19 development processes into three typical modes of immune responses, correlated with the clinical classification of mild & moderate, severe and critical patients. We found that the immune efficacy (the ability of host to clear virus and kill infected cells) and the lymphocyte supply (the abundance and pool of naïve T and B cell) play important roles in the dynamic process and determine the clinical outcome, especially for the severe and critical patients. Furthermore, we put forward possible treatment strategies for the three typical modes of immune response. We hope our results can help to understand the dynamical mechanism of the immune response against SARS-CoV-2 infection, and to be useful for the treatment strategies and vaccine design.
Early analysis of a potential link between viral load and the N501Y mutation in the SARS-COV-2 spike protein
Authors: Golubchik Tanya , Lythgoe Katrina A. , Hall Matthew , Ferretti Luca , Fryer Helen R. , MacIntyre-Cockett George , de Cesare Mariateresa , Trebes Amy , Piazza Paolo , Buck David , Todd John A. ,   The COVID-19 Genomics UK (COG-UK) consortium, Fraser Christophe , Bonsall David
Published: January 2021

A new variant of SARS-CoV-2 has emerged which is increasing in frequency, primarily in the South East of England (lineage B.1.1.7 (1); VUI-202012/01). One potential hypothesis is that infection with the new variant results in higher viral loads, which in turn may make the virus more transmissible. We found higher (sequence derived) viral loads in samples from individuals infected with the new variant with median inferred viral loads were three-fold higher in individuals with the new variant. Most of the new variants were sampled in Kent and Greater London. We observed higher viral loads in Kent compared to Greater London for both the new variant and other circulating lineages. Outside Greater London, the variant has higher viral loads, whereas within Greater London, the new variant does not have significantly higher viral loads compared to other circulating lineages. Higher variant viral loads outside Greater London could be due to demographic effects, such as a faster variant growth rate compared to other lineages or concentration in particular age-groups. However, our analysis does not exclude a causal link between infection with the new variant and higher viral loads. This is a preliminary analysis and further work is needed to investigate any potential causal link between infection with this new variant and higher viral loads, and whether this results in higher transmissibility, severity of infection, or affects relative rates of symptomatic and asymptomatic infection

Document Description and Purpose

This is an updated report submitted to NERVTAG in December 2020 as part of urgent investigations into the new variant of SARS-COV-2 (VUI-202012/01). It makes full use of (and is restricted to) all sequence data and associated metadata available to us at the time this original report was submitted and remains provisional. Under normal circumstances more genomes and metadata would be obtained and included before making this report public. We will update this preprint when more genomes and metadata are available and before submitting for peer review.
Prostate cancer castrate resistant progression usage of non-canonical androgen receptor signaling and ketone body fuel
Authors: Labanca Estefania , Bizzotto Juan , Sanchis Pablo , Yang Jun , Shepherd Peter D.A. , Paez Alejandra , Antico-Arciuch Valeria , Anselmino Nicolas , Lage-Vickers Sofia , Hoang Anh G. , Titus Mark , Efstathiou Eleni , Cotignola Javier , Araujo John , Logothetis Christopher , Vazquez Elba , Navone Nora , Gueron Geraldine
Published: January 2021

Prostate cancer (PCa) that progresses after androgen deprivation therapy (ADT) remains incurable. The intricacy of metabolic pathways associated with PCa progression spurred us to develop a metabolism-centric analysis. Using PCa patient-derived xenografts (PDXs) we assessed the metabolic changes after castration of tumor-bearing mice. We found that relapsed tumors had a significant increase in fatty acids and ketone body content compared with baseline. We confirmed that critical ketogenic/ketolytic enzymes (ACAT1, OXCT1, BDH1) were significantly augmented after castrate-resistant progression. Further, these enzymes are increased in the human donor tissue after progressing to ADT.

Increased ACAT1 and OXCT1 was also observed for a subset of PCa patients that relapsed with low AR and ERG expression. These factors were associated with decreased biochemical relapse and progression free survival. In summary, our studies reveal the key metabolites fueling castration resistant progression in the context of a partial or complete loss of AR dependence.
Dynamical Pool-Size Optimization for the SARS-CoV-2 PCR Test
Authors: Smirnov Juri , Fenner Thomas
Published: January 2021

In this work, we put forward a novel test strategy, that allows to significantly increase the test capacity for SARS-CoV-2. The test strategy is based on an a priory risk assessment scheme, that allows to dynamically find and adapt an optimal clustering size of test pools. We, furthermore, suggest a method to overcome the efficiency loss of test clustering by avoiding concentration losses in the test samples. We validated our method with several thousand probe pools performing RT-PCR tests, and found it highly effective.
Scalable cardiovascular risk assessment using artificial intelligence-enabled event adjudication and widely available hematologic predictors
Authors: Truslow James G. , Goto Shinichi , Homilius Max , Mow Christopher , Higgins John M. , MacRae Calum A. , Deo Rahul C.
Published: January 2021

Introduction

Researchers routinely evaluate novel biomarkers for incorporation into clinical risk models. Although of potential benefit, such emerging markers, which are often costly or not yet commercially available, are unlikely to enable the scalable risk assessment needed for population health strategies. In contrast, the ideal inputs for population approaches would be those already widely available for most patients. We hypothesized that simple hematologic markers, available in an outpatient complete blood count without differential, would be useful to develop risk models for cardiovascular events.

Methods

Using routine laboratory measurements as predictors and neural network-based automated event adjudication of 1,072,348 discharge summaries, we developed and validated models for prediction of heart attack, ischemic stroke, heart failure hospitalization, revascularization, and all-cause mortality.

Results

Models with hematology indices alone showed Harrell’s concordance index ranging from 0.60–0.80 on an external validation set. Hematology indices added significantly in terms of discrimination and calibration performance compared to models using only demographic data and diagnostic codes for coronary artery disease, heart failure, and ischemic stroke, with the concordance index of resulting models in the range 0.75–0.85 on an external validation set. Predictive features varied by outcome, and included red blood cell, leukocyte, and platelet indices.

Conclusion

We conclude that low-cost ubiquitous inputs, if biologically informative, can provide population-level readouts of risk.
Impact of CancelRx on Discontinuation of Controlled Substance Prescriptions
Authors: Watterson Taylor L. , Stone Jamie A , Gilson Aaron , Brown Roger , Xiong Ka Z , Schiefelbein Anthony , Ramly Edmond , Kleinschmidt Peter , Semanik Michael , Craddock Lauren , Pitts Samantha , Woodroof Taylor , Chui Michelle
Published: January 2021

Objective

To assess how controlled substance medication discontinuations were communicated over time

Data Sources

Secondary data from a midwestern academic health system electronic health record and pharmacy platform were collected 12-months prior to CancelRx implementation and for 12-months post implementation.

Study Design

The study utilized an interrupted time series analysis (ITSA) to capture the proportion of controlled substance medications that were cancelled in the clinic’s electronic health record and also cancelled in the pharmacy’s dispensing software. The ITSA plotted the proportion of successful cancellation messages over time, particularly after the health system’s implementation of CancelRx, a novel technology.

Data Collection/Extraction

Data were extracted from the EHR and pharmacy records for patients aged 18+ who had a controlled substance discontinued by a health system provider. Information collected included patient demographics, drug information (name, dose), and dates discontinued in the clinic and pharmacy records.

Principal Findings

After CancelRx implementation there was a significant increase in the proportion of discontinued controlled substance medications that were communicated to the pharmacy.

Conclusions

This study demonstrates the role that technology can play in promoting controlled substance policy and medication safety.
Proline-rich Extensin-like Receptor Kinases PERK5 and PERK12 are involved in Pollen Tube Growth
Authors: Borassi Cecilia , Sede Ana R. , Mecchia Martin A. , Mangano Silvina , Marzol Eliana , Denita-Juarez Silvina P. , Salgado Salter Juan D. , Velasquez Silvia M. , Muschietti Jorge P. , Estevez José M.
Published: January 2021

Background

Cell wall integrity plays an essential role during polarized cell growth typical of pollen tubes and root hairs. Proline-rich Extensin-like Receptor Kinases (PERK) belong to the hydroxyproline-rich glycoprotein (HRGP) superfamily of cell surface glycoproteins.

Results

Here, we identified two PERKs from Arabidopsis thaliana, PERK5 and PERK12 highly expressed in mature pollen. Pollen tube growth was impaired in the single and double perk5-1 perk12-1 loss of function mutants, with a moderate impact on seed production. When the segregation of self- and reciprocal-crosses of the perk5-1, perk5-2 and perk12-1 single mutants, and reciprocal-crosses of the perk5-1 perk12-1 double mutant were carried out, a male gametophytic defect was found, indicating that perk5-1 and perk12-1 mutants carry defective pollen tubes, resulting in deficient pollen transmission. Furthermore, double perk5-1 perk12-1 mutants show excessive accumulation of pectins and cellulose at the cell wall pollen of the tube tip. In addition, an upregulation of cytoplasmic ROS levels were detected by using 2,7-dichlorofluorescein diacetate probe (H2DCF-DA), and in agreement, similar results were obtained with HyPer, a genetically encoded YFP-based radiometric sensor, which is used to follow the production of hydrogen peroxide (H2O2). Single and double perk5-1 perk12-1 mutants show higher levels of cytoplasmic H2O2 in their pollen tube tips.

Conclusions

Taken together, our results suggest that PERK5 and PERK12 are necessary for proper pollen tube growth highlighting their role on cell wall assembly and ROS homeostasis.
In silicoapproach on drug repurposing - Antimalarial drugs against HIV-1 protease
Authors: Arulanandam Charli Deepak
Published: January 2021

Acquired Immunodeficiency Syndrome (AIDS), belonging to the retrovirus family is one of the most devastating contagious diseases of this century. Most of the available approved drugs are small molecules which are used in antiretroviral therapy (ART) that trigger the therapeutic response through binding to a targeted protein, HIV-1 protease (PR). This protein represents the most important antiretroviral drug target due to its key role in viral development inhibition. Computational tools using computer-aided technologies have proven useful in accelerating the drug discovery. In this study we evaluated selected FDA (USA) approved antimalarial drugs against HIV-1 protease to find a potential inhibitor candidate for HIV-1 PR (PDB 6DJ1). Binding affinities and Ki inhibition constant of an AutoDock 4.2 study suggest that of all assessed antimalarial agents, Lumefantrine (LUM) would be a most promising HIV-1 PR inhibitor.
Raman spectroscopy on microcalcifications reveals peculiar differences between male and female breast cancer
Authors: Caldarone Alessandro , Piccotti Francesca , Morasso Carlo , Truffi Marta , Sottotetti Federico , Guerra Chiara , Albasini Sara , Agozzino Manuela , Villani Laura , Corsi Fabio
Published: January 2021

Microcalcifications (MCs) are important disease markers for breast cancer. Many studies were conducted on their characterization in female breast cancer (FBC), but no information is available on their composition in male breast cancer (MBC). Raman spectroscopy (RS) is a molecular spectroscopy technique that can explore the biochemical composition of MCs rapidly and without requiring any staining protocol. We here compared, by Raman spectroscopy, the MCs identified on breast cancer pieces from male and female patients. In this study, we used Raman spectroscopy to analyse 41 microcalcifications from 5 invasive MBC patients and 149 MCs from 14 invasive FBC patients. Our findings show that hydroxyapatite is the most abundant type of calcium both in MBC and FBC. However, some differences in the amount and distribution of calcium minerals are present between the two groups. Besides, we observed that MCs in MBC have a higher amount of organic material (collagen) than FBC.

This study provides the first overview of the composition of microcalcifications present in MBC and suggests that they have several specific features. Our result support the need for studies specifically designed to the understanding of MBC.
Diet induced hyperlipidemia confers resistance to standard therapy in pancreatic cancer by selecting for “tumor protective” microbial metabolites and treatment refractory cells
Authors: Kesh Kousik , Mendez Roberto , Mateo-Victoriano Beatriz , Garrido Vanessa T , Durden Brittany , Gupta Vineet K , Reyes Alfredo Oliveras , Datta Jashodeep , Merchant Nipun , Banerjee Santanu , Banerjee Sulagna
Published: January 2021

Obesity causes a number of systemic alterations including chronic inflammation and changes in gut microbiome. However, whether these actively contribute to poor survival and therapy resistance in patients with pancreatic cancer remain undetermined. Our current study shows that high fat diet fed pancreatic tumor bearing mice do not respond to standard of care therapy with gemcitabine and paclitaxel when compared to corresponding control diet fed mice. Upon fecal matter transplant from control mice to high fat diet fed mice, the tumors became sensitive to standard of care therapy and showed extensive cell death. Analysis of gut microbiome showed an enrichment of queuosine (Q) producing bacteria in high fat diet fed mice and an enrichment of S-adenosyl methionine (SAM) producing bacteria in control diet fed mice. Further, treatment of high fat diet fed animals with SAM recapitulated the observation with lean to obese fecal matter transplant. Additionally, treatment of pancreatic and colon cancer cell lines in vitro with Q promoted resistance to the paclitaxel and oxaliplatin respectively, while treatment with SAM promoted sensitivity to these drugs. Treatment of pancreatic cancer cells with Q showed upregulation PRDX1, that is involved in oxidative stress protection. Analysis of tumor tissues in high fat diet fed mice showed high PRDX1, low apoptosis and increased proliferation, which were reversed upon treatment with SAM as well as by lean to obese fecal matter transplant. In parallel, high fat diet fed mice showed increase in CD133+ treatment refractory population compared to the control animals. Interestingly, treatment with Qin vitrodid not enrich for CD133+ population, indicating that Q mediated protection from cell death was independent of enrichment of treatment refractory cells.

These observations indicated that microbial metabolite Q accumulated in high fat diet fed mice protected tumors from chemotherapy induced oxidative stress by upregulating PRDX1. This protection could be reversed by treatment with SAM. We conclude that relative concentration of S-adenosyl methionine and queuosine in fecal samples of pancreatic cancer patients can be indicative of therapy response in this disease.
Physicians’ Reactions to COVID-19: The Results of an International Internet Survey
Authors: Aneja Parul , Singh Inderjit , Singh Bhupinder , Kundi Pardeep Singh , Singh Inderbir , Kathiravan Sanjana , Singh Shubh Mohan
Published: January 2021

Objectives

Physicians across the world have been disproportionately affected by the COVID-19 pandemic. This study was designed and conducted to assess the emotional, cognitive, and behavioural reactions of physicians to the initial phase of the COVID-19 pandemic.

Materials and methods

An online survey questionnaire using the google forms platform was constructed by the authors. The items in the questionnaire were based on clinical experience, relevant literature review and discussion with peers. A list of issues that were deemed as essential components of the experience of the pandemic relevant to physicians was arrived at. Thereafter these issues were operationalized into question form and hosted on the google forms platform. The link to this questionnaire was circulated by the authors among their peer groups in the month of April 2020.

Results

We received 295 responses and 3 were unusable. Most of the responses were from India, the United States of America, Australia, Canada and the United Kingdom. About 60% of the respondents identified themselves as frontline and had a decade of clinical experience. Most respondents reported being anxious due to the pandemic and also observed the same in their peers and families. A majority also observed changes in behaviour in self and others and advanced a variety of reasons and concerns. A sense of duty was the most commonly employed coping mechanism.

Conclusion

Physicians are not immune from information and misinformation, or cues in the environment. Behavioural choices are not always predicted by knowledge but by a combination of knowledge, emotional state, personality and environment. Healthcare settings need to be ready for emergencies and should focus on reducing uncertainty in physicians. These factors may also be gainfully used in the mental health promotion of physicians in COVID-19 care roles.