bluuebunny/crossref_metadata_2025 huggingface dataset:
Second-Reprise Opening Schemas in Bach’s Binary Movements
Authors: Brody Christopher
Published: March 2021

A harmonic pattern, termed the V–I schema, is shown to structure most of the second-reprise openings in Bach’s binary movements. This pattern combines cross-repertoire harmonic consistency with context-dependent prolongational variability, a juxtaposition that causes intractable contradictions to emerge within Schenkerian theory. The schematic aspect to early eighteenth-century tonality suggested by this feature is expanded to include two additional second-reprise openings, the V–vi schema and the in-III opening. A staple of most Baroque composers’ harmonic vocabulary, the V–I schema declined in the later eighteenth century, incompatible with the new prevalence of rounded binary form.
People confabulate with high confidence when their decisions are supported by weak internal variables
Authors: Rebouillat Benjamin , Leonetti Jean Maurice , Kouider Sid
Published: March 2021

People can introspect on their internal state and report the reasons driving their decisions but choice blindness (CB) experiments suggest that this ability can sometimes be a retrospective illusion. Indeed, when presented with deceptive cues, people justify choices they did not make in the first place, suggesting that external cues largely contribute to introspective processes. Yet, it remains unclear what are the respective contributions of external cues and internal decision variables in forming introspective report. Here, using a brain–computer interface, we show that internal variables continue to be monitored but are less impactful than deceptive external cues during CB episodes. Moreover, we show that deceptive cues overturn the classical relationship between confidence and accuracy: introspective failures are associated with higher confidence than genuine introspective reports. We tracked back the origin of these overconfident confabulations by revealing their prominence when internal decision evidence is weak and variable. Thus, introspection is neither a direct reading of internal variables nor a mere retrospective illusion, but rather reflects the integration of internal decision evidence and external cues, with CB being a special instance where internal evidence is inconsistent.
Chemotherapy for adult patients with spinal cord gliomas
Authors: Gramatzki Dorothee , Felsberg Jörg , Hentschel Bettina , Bähr Oliver , Westphal Manfred , Schackert Gabriele , Tonn Jörg Christian , Herrlinger Ulrich , Loeffler Markus , Pietsch Torsten , Steinbach Joachim Peter , Reifenberger Guido , Roth Patrick , Weller Michael
Published: March 2021

Background

The incidence of spinal cord gliomas, particularly in adults is low, and the role of chemotherapy has remained unclear.

Methods

We performed a multicenter, retrospective study of 21 patients diagnosed with spinal cord glioma who received chemotherapy at any time during the disease course. Benefit from chemotherapy was estimated by magnetic resonance imaging. Data on radiotherapy were taken into consideration.

Results

Thirteen patients were diagnosed with astrocytic gliomas World Health Organization (WHO) grades 1-4, the remaining eight patients with ependymomas WHO grades 1 or 3. Most patients had more than one neurosurgical intervention. Median age at time of first chemotherapy was 33 years (range 21-67 years). Seven patients had chemotherapy combined with radiotherapy as first-line treatment. Two patients had chemoradiotherapy at recurrence, without prior tumor-specific treatment beyond surgery. One patient received chemotherapy alone as first-line treatment and 2 patients had chemotherapy alone at recurrence, without prior treatment. Nine patients had received radiation therapy at an earlier time and chemotherapy was given at time of further recurrences. Best responses in astrocytomas were as follows: chemotherapy alone—2 stable disease (SD) and 3 progressive disease (PD); chemoradiotherapy—1 complete response, 3 SD, and 4 PD. Best responses in ependymomas were as follows: chemotherapy alone—1 partial response, 5 SD, and 1 PD; chemoradiotherapy—1 SD.

Conclusions

Spinal cord gliomas represent a heterogeneous group of tumors. Survival outcomes in response to chemotherapy in adult spinal cord glioma patients vary substantially, but individual patients appear to derive benefit from chemotherapy.
The intestinal luminal sources of α-synuclein: a gastroenterologist perspective
Authors: Lerner Aaron
Published: March 2021

Parkinson’s disease is characterized by nonmotor/motor dysfunction, midbrain dopaminergic neuronal death, and α-synuclein (aSN) deposits. The current hypothesis is that aSN accumulates in the enteric nervous system to reach the brain. However, invertebrate, vertebrate, and nutritional sources of aSN reach the luminal compartment. Submitted to local amyloidogenic forces, the oligomerized proteins’ cargo can be sensed and sampled by a specialized mucosal cell to be transmitted to the adjacent enteric nervous system, starting their upward journey to the brain. The present narrative review extends the current mucosal origin of Parkinson’s disease, presenting the possibility that the disease starts in the intestinal lumen. If substantiated, eliminating the nutritional sources of aSN (eg, applying a vegetarian diet) might revolutionize the currently used dopaminergic pharmacologic therapy.
Tedizolid vs Linezolid for the Treatment of Nontuberculous Mycobacteria Infections in Solid Organ Transplant Recipients
Authors: Poon Yi Kee , La Hoz Ricardo M , Hynan Linda S , Sanders James , Monogue Marguerite L
Published: March 2021

Background

Treatment options for nontuberculous mycobacteria (NTM) infections are limited by the pathogen’s intrinsic resistance profile and toxicities. Tedizolid and linezolid display in vitro activity against NTM species. However, safety data and treatment outcomes are limited in the solid organ transplant (SOT) population.

Methods

This was a single-center retrospective cohort study of adult SOT recipients receiving linezolid or tedizolid for an NTM infection from January 1, 2010, to August 31, 2019. The primary outcome compared the hematologic safety profiles of tedizolid vs linezolid. We also described nonhematological adverse drug events (ADEs) and therapy discontinuation rates. In an exploratory analysis, we assessed symptomatic microbiologic and clinical outcomes in those receiving tedizolid or linezolid for at least 4 weeks.

Results

Twenty-four patients were included (15 tedizolid, 9 linezolid). No differences were identified comparing the effects of tedizolid vs linezolid on platelet counts, absolute neutrophil counts (ANCs), and hemoglobin over 7 weeks using mixed-effects analysis of variance models. ANC was significantly decreased in both groups after 7 weeks of therapy (P = .04). Approximately 20% of patients in each arm discontinued therapy due to an ADE. Seven of 12 (58%) and 2 of 3 (67%) patients were cured or clinically cured with tedizolid- and linezolid-containing regimens, respectively.

Conclusions

This study suggests no significant safety benefit of tedizolid over linezolid for the treatment of NTM infections in SOT recipients. Tedizolid or linezolid-containing regimens demonstrated a potential benefit in symptomatic and microbiologic improvement. Larger cohorts are needed to further delineate the comparative role of linezolid and tedizolid for the treatment of NTM infections in SOT recipients.
Drug Resistance in HIV-Positive Adults During the Initial Year of Antiretroviral Treatment at Ethiopian Health Centers
Authors: Reepalu Anton , Arimide Dawit A , Balcha Taye T , Yeba Habtamu , Zewdu Adinew , Medstrand Patrik , Björkman Per
Published: March 2021

Background

The increasing prevalence of antiretroviral drug resistance in Sub-Saharan Africa threatens the success of HIV programs. We have characterized patterns of drug resistance mutations (DRMs) during the initial year of antiretroviral treatment (ART) in HIV-positive adults receiving care at Ethiopian health centers and investigated the impact of tuberculosis on DRM acquisition.

Methods

Participants were identified from a cohort of ART-naïve individuals aged ≥18 years, all of whom had been investigated for active tuberculosis at inclusion. Individuals with viral load (VL) data at 6 and/or 12 months after ART initiation were selected for this study. Genotypic testing was performed on samples with VLs ≥500 copies/mL obtained on these occasions and on pre-ART samples from those with detectable DRMs during ART. Logistic regression analysis was used to investigate the association between DRM acquisition and tuberculosis.

Results

Among 621 included individuals (110 [17.5%] with concomitant tuberculosis), 101/621 (16.3%) had a VL ≥500 copies/mL at 6 and/or 12 months. DRMs were detected in 64/98 cases with successful genotyping (65.3%). DRMs were detected in 7/56 (12.5%) pre-ART samples from these individuals. High pre-ART VL and low mid-upper arm circumference were associated with increased risk of DRM acquisition, whereas no such association was found for concomitant tuberculosis.

Conclusions

Among adults receiving health center–based ART in Ethiopia, most patients without virological suppression during the first year of ART had detectable DRM. Acquisition of DRM during this period was the dominant cause of antiretroviral drug resistance in this setting. Tuberculosis did not increase the risk of DRM acquisition.
Prolonged activated partial thromboplastin time secondary to factor XII deficiency in two surgical patients
Authors: Moiz Bushra , Sadiq Muhammed Wahhaab , Javed Muhammad Abdullah , Jafry Baqir Hasan , Anees Muhammad
Published: March 2021

Factor XII (FXII) plays a pivotal role in hemostasis, inflammation and complement system. Its deficiency is usually an incidental finding in an otherwise asymptomatic patient who is identified during his/her routine preoperative blood work. This study aimed in evaluating the clinical course of the surgical patients having FXII deficiency. Information regarding demographics, laboratory tests and management of patients was obtained through medical chart and in-house integrated laboratory management system whereas the medical literature was searched through PubMed®. During the study period, two patients were consulted for FXII deficiency prior to the various surgical procedures. Both patients had uneventful surgeries without any thrombotic events while hemorrhage observed in one patient was secondary to obstetric complications. With the limited evidence today, it is concluded that patients having FXII deficiency are not at increased risk of bleeding, thrombosis or infections during surgery, but a personalized approach is needed for planning an appropriate perioperative management.
Evaluation and management of a spontaneous corneal rupture secondary to pellucid marginal degeneration, using swept-source anterior segment optical coherence tomography
Authors: Papamlichael Esther , Logeswaran Abison , Papastefanou Vasilios P , Watson Martin , Coombes Andrew
Published: March 2021

We describe a case of bilateral spontaneous corneal perforation secondary to pellucid marginal degeneration and present the associated swept-source anterior segment optical coherence tomography (SS-ASOCT) findings and management principles used.

A 47-year-old woman presented with ocular pain, redness, foreign body sensation and clear discharge in the right eye in 2017 and with very similar symptoms in 2019 in the left eye. Clinically she had a corneal perforation at the inferior cornea with associated loss of anterior chamber volume. Corneal topography demonstrated peripheral thinning and steepening in the contralateral eye. ASOCT images revealed full-thickness perforation, iridocorneal touch and iris stranding. The patient was managed with a combination of contact bandaging and corneal gluing.

SS-ASOCT is a useful adjunctive tool in the clinical assessment and evaluation of spontaneous corneal perforation. Alongside the clinical evaluation, it can be used to monitor the clinical response.
Endoscopic Posterior Approach for Cervicothoracic and Upper Thoracic Foraminotomies: 2-Dimensional Operative Video
Authors: Kim Robert B , Kundu Bornali , Mahan Mark A
Published: March 2021

Lower cervical and cervicothoracic radiculopathies can be challenging to treat through an anterior approach in patients with short-statured necks. With unilateral pathology, a posterior foraminotomy affords preservation of motion and avoids risks to anterior structures; yet, traditional open or even tubular retractor-based open systems are associated with postoperative muscle pain. Endoscopic approaches reduce muscle retraction and resection and are associated with shorter recovery time. This video demonstrates the endoscopic technique for performing cervicothoracic and thoracic foraminotomies. We present the case of a patient with severe left-hand weakness, particularly in grasp and hand intrinsic muscles. The differential diagnosis included a combined median and ulnar neuropathy, lower trunk plexopathy, medial cord plexopathy, thoracic outlet syndrome, and combined C8 and T1 radiculopathies. Imaging did not show brachial plexus pathology; instead, severe foraminal narrowing at the C8 and T1 roots was noted. We performed a fully endoscopic approach to decompress 2 levels of foraminal stenosis on the left side. Because the levels were adjacent, we operated through a single incision. Recovery of motor-evoked potentials to the abductor pollicis brevis was identified intraoperatively.

The patient consented to the procedure and publication.
Alcohol affordability: implications for alcohol price policies. A cross-sectional analysis in middle and older adults from UK Biobank
Authors: Moore Simon C , Orpen Bella , Smith Jesse , Sarkar Chinmoy , Li Chenlu , Shepherd Jonathan , Bauermeister Sarah
Published: March 2021

Background

Increasing the price of alcohol reduces alcohol consumption and harm. The role of food complementarity, transaction costs and inflation on alcohol demand are determined and discussed in relation to alcohol price policies.

Methods

UK Biobank (N = 502,628) was linked by region to retail price quotes for the years 2007 to 2010. The log residual food and alcohol prices, and alcohol availability were regressed onto log daily alcohol consumption. Model standard errors were adjusted for clustering by region.

Results

Associations with alcohol consumption were found for alcohol price (β = −0.56, 95% CI, −0.92 to −0.20) and availability (β = 0.06, 95% CI, 0.04 to 0.07). Introducing, food price reduced the alcohol price consumption association (β = −0.26, 95% CI, −0.50 to −0.03). Alcohol (B = 0.001, 95% CI, 0.0004 to 0.001) and food (B = 0.001, 95% CI, 0.0005 to 0.0006) price increased with time and were associated (ρ = 0.57, P < 0.001).

Conclusion

Alcohol and food are complements, and the price elasticity of alcohol reduces when the effect of food price is accounted for. Transaction costs did not affect the alcohol price consumption relationship. Fixed alcohol price policies are susceptible to inflation.
Modified poly(methyl methacrylate) bone cement in the treatment of Kümmell disease
Authors: Zhu Jinjin , Yang Shuhui , Yang Yute , Yao Teng , Liu Gang , Fan Shunwu , Zhao He , Cui Fuzhai , Wang Xiumei , Jiang Guoqiang , Fang Xiangqian
Published: March 2021

Kümmell disease (KD) causes serious vertebral body collapse in patients. However, only a few case reports have been conducted and the number of patients with KD investigated was limited. Additionally, the frequently used poly(methyl methacrylate) (PMMA) bone cement for KD is limited by excessive modulus and poor biocompatibility. Herein, we aimed to modify PMMA bone cement with mineralized collagen (MC), and compare the clinical effects, image performance and finite element analysis between the modified bone cement and PMMA bone cement for the treatment of phase I and II KD. Thirty-nine KD patients treated with PMMA bone cement and 40 KD patients treated with MC-modified PMMA bone cement from June 2015 to March 2017 were retrospectively analyzed. The surgical procedure, intraoperative blood loss, hospital stay and complications were compared between different groups. Visual analog scale, Oswestry disability index, anterior vertebral height, posterior vertebral height, computed tomography value, adjacent vertebral re-fracture, Cobb angle and wedge-shaped correction angle were evaluated. Additionally, the representative sample was selected for finite element analysis. We found that the MC-modified PMMA bone cement could achieve the same effect as that of PMMA bone cement and was associated with better vertebral height restoration in the long term.
IDAC-ALPHA: AN ALPHA DOSIMETRY SOFTWARE FOR NORMAL ORGANS AND TISSUES
Authors: Andersson M , Kluge A , Meyer T , Koumarianou E , Mattsson S
Published: March 2021

Radiopharmaceuticals have been used for the treatment of various forms of cancer since the 1940s. In recent years, the advantages of alpha emitting radionuclides have emerged as a favourable treatment option. However, most alpha emitting radionuclides have long decay chains with long-lived daughter radionuclides. This leads to uncertainties in the dosimetry for normal organs and tissues, when established dosimetry models are employed. The aim of this project is to assign each progeny its own biokinetic behaviour. The novel dosimetry model was applied to 223Ra-dichloride, frequently used for the treatment of patients with metastatic bone disease from castration-resistant prostate cancer. In this dosimetry model, individual biokinetics for each daughter radionuclide was included. This resulted in a decrease in absorbed dose to bone surfaces and red marrow and increased absorbed dose to liver and kidney, when compared with dosimetry models assuming that the daughter nuclides follow the biokinetics of the parent radionuclide.
Distinguishing sleep from wake with a radar sensor: a contact-free real-time sleep monitor
Authors: Heglum Hanne Siri Amdahl , Kallestad Håvard , Vethe Daniel , Langsrud Knut , Sand Trond , Engstrøm Morten
Published: March 2021

This work aimed to evaluate whether a radar sensor can distinguish sleep from wakefulness in real time. The sensor detects body movements without direct physical contact with the subject and can be embedded in the roof of a hospital room for completely unobtrusive monitoring. We conducted simultaneous recordings with polysomnography, actigraphy, and radar on two groups: healthy young adults (n = 12, four nights per participant) and patients referred to a sleep examination (n = 28, one night per participant). We developed models for sleep/wake classification based on principles commonly used by actigraphy, including real-time models, and tested them on both datasets. We estimated a set of commonly reported sleep parameters from these data, including total-sleep-time, sleep-onset-latency, sleep-efficiency, and wake-after-sleep-onset, and evaluated the inter-method reliability of these estimates. Classification results were on-par with, or exceeding, those often seen for actigraphy. For real-time models in healthy young adults, accuracies were above 92%, sensitivities above 95%, specificities above 83%, and all Cohen's kappa values were above 0.81 compared to polysomnography. For patients referred to a sleep examination, accuracies were above 81%, sensitivities about 89%, specificities above 53%, and Cohen's kappa values above 0.44. Sleep variable estimates showed no significant intermethod bias, but the limits of agreement were quite wide for the group of patients referred to a sleep examination. Our results indicate that the radar has the potential to offer the benefits of contact-free real-time monitoring of sleep, both for in-patients and for ambulatory home monitoring.
Association of Citrus Virus A to Citrus Impietratura Disease Symptoms
Authors: Beris Despoina , Ioanna Malandraki , Vassilakos Nikon , Theologidis Ioannis , Rampou Aggeliki , Kektsidou Oxana , Massart Sebastien , Varveri Christina
Published: March 2021

Citrus impietratura disease (CID) is a graft transmissible, virus-like disease observed in old-line citrus trees; its characteristic symptom is the appearance of gum in the albedo of the affected fruits. To identify the causal agent of the disease, high-throughput sequencing (HTS) was performed on symptomatic orange fruits. The analysis of the obtained data revealed in all samples mixed infections of viroids commonly found in citrus trees together with the recently described citrus virus A (CiVA). Examination of additional symptomatic fruits with conventional reverse transcription PCR led to the identification of a single CiVA infection in one tree, which was verified by HTS. Indexing of the single CiVA-infected tree on indicator plants resulted in the appearance of characteristic symptoms in the leaves that were correlated with virus accumulation. Moreover, a comparative analysis among symptomatic and asymptomatic fruits derived from the same trees was performed and included the single CiVA-infected orange tree. The analysis revealed a positive correlation between the appearance of symptoms and the accumulation of CiVA RNAs. To facilitate CiVA detection during certification programs of propagation material, a quantitative RT-PCR targeting the movement protein of the virus was developed and evaluated for reliable and sensitive detection of the virus. To the best of our knowledge this is the first study that associates CiVA with the appearance of CID symptoms.
Lack of an Intron in Cytochrome b and Overexpression of Sterol 14α-Demethylase Indicate a Potential Risk for QoI and DMI Resistance Development in Neophysopella spp. on Grapes
Authors: Santos Ricardo F. , Amorim Lilian , Wood Ana K. M. , Bibiano Líllian B. J. , Fraaije Bart A.
Published: March 2021

Asian grapevine leaf rust, caused by Neophysopella meliosmae-myrianthae and N. tropicalis, is often controlled by quinone outside inhibitor (QoI) and demethylation inhibitor (DMI) fungicides in Brazil. Here, we evaluated the sensitivity of 55 Neophysopella spp. isolates to pyraclostrobin (QoI) and tebuconazole (DMI). To elucidate the resistance mechanisms, we analyzed the sequences of the cytochrome b (CYTB) and cytochrome P450 sterol 14α-demethylase (CYP51) target proteins of QoI and DMI fungicides, respectively. The CYP51 expression levels were also determined in a selection of isolates. In leaf disc assays, the mean 50% effective concentration (EC50) value for pyraclostrobin was about 0.040 µg/ml for both species. CYTB sequences were identical among all 55 isolates, which did not contain an intron immediately after codon 143. No amino acid substitution was identified at codons 129, 137, and 143. The mean EC50 value for tebuconazole was 0.62 µg/ml for N. tropicalis and 0.46 µg/ml for N. meliosmae-myrianthae, and no CYP51 sequence variation was identified among isolates of the same species. However, five N. meliosmae-myrianthae isolates grew on leaf discs treated at 10 µg/ml tebuconazole, and these were further exposed to tebuconazole selection pressure. Tebuconazole-adapted laboratory isolates of N. meliosmae-myrianthae showed an eight- to 25-fold increase in resistance after four rounds of selection that was not associated with CYP51 target alterations. In comparison with sensitive isolates, CYP51 expression was induced in the presence of tebuconazole in three out of four tebuconazole-adapted isolates tested. These results suggest a potential risk for QoI and DMI resistance development in Neophysopella spp.
Targeting alveolar‐specific succinate dehydrogenase A attenuates pulmonary inflammation during acute lung injury
Authors: Vohwinkel Christine U. , Coit Ethan J. , Burns Nana , Elajaili Hanan , Hernandez‐Saavedra Daniel , Yuan Xiaoyi , Eckle Tobias , Nozik Eva , Tuder Rubin M. , Eltzschig Holger K.
Published: March 2021

Acute lung injury (ALI) is an inflammatory lung disease, which manifests itself in patients as acute respiratory distress syndrome (ARDS). Previous studies have implicated alveolar‐epithelial succinate in ALI protection. Therefore, we hypothesized that targeting alveolar succinate dehydrogenase SDH A would result in elevated succinate levels and concomitant lung protection. Wild‐type (WT) mice or transgenic mice with targeted alveolar‐epithelial Sdha or hypoxia‐inducible transcription factor Hif1a deletion were exposed to ALI induced by mechanical ventilation. Succinate metabolism was assessed in alveolar‐epithelial via mass spectrometry as well as redox measurements and evaluation of lung injury. In WT mice, ALI induced by mechanical ventilation decreased SDHA activity and increased succinate in alveolar‐epithelial. In vitro, cell‐permeable succinate decreased epithelial inflammation during stretch injury. Mice with inducible alveolar‐epithelial Sdha deletion (Sdhaloxp/loxp SPC‐CreER mice) revealed reduced lung inflammation, improved alveolar barrier function, and attenuated histologic injury. Consistent with a functional role of succinate to stabilize HIF, Sdhaloxp/loxp SPC‐CreER experienced enhanced Hif1a levels during hypoxia or ALI. Conversely, Hif1aloxp/loxp SPC‐CreER showed increased inflammation with ALI induced by mechanical ventilation. Finally, wild‐type mice treated with intra‐tracheal dimethlysuccinate were protected during ALI. These data suggest that targeting alveolar‐epithelial SDHA dampens ALI via succinate‐mediated stabilization of HIF1A. Translational extensions of our studies implicate succinate treatment in attenuating alveolar inflammation in patients suffering from ARDS.
Abortion Waiting Periods and Decision Certainty Among People Searching Online for Abortion Care
Authors: Jovel Iris , Cartwright Alice F. , Ralph Lauren , Upadhyay Ushma D.
Published: March 2021

OBJECTIVE:

Many U.S. states mandate counseling and a waiting period before abortion, which often necessitates two separate clinic visits. These laws purport to ensure individuals are certain about their abortion decision. We examined whether exposure to these laws is associated with increased decision certainty.

METHODS:

The Google Ads Abortion Access Study is a prospective study of pregnant people considering abortion recruited when searching online using abortion care-related keywords. Eligible participants, who represented all 50 U.S. states, completed baseline and 4-week follow-up surveys. We measured decision certainty using the Decisional Conflict Scale (scores range from 0 to 100; higher scores reflect lower certainty). We used a multivariable linear mixed model to examine the association between living in states with waiting periods, two-visit requirements, or both and changes in decision certainty. We also compared baseline, follow-up, and changes in decision certainty by whether the pregnancy was ongoing or not at follow-up.

RESULTS:

The analytic sample included 750 participants who contributed relevant baseline and follow-up data. At follow-up, 396 participants had an abortion, and 354 had not. There was no significant increase in decision certainty for participants in states with waiting period laws (mean change score −1.0, 95% CI −2.8 to 2.8). In adjusted models, still seeking an abortion at 4-week follow-up was associated with decreased certainty (mean change score 8.05, 95% CI 5.13–10.97). Those still seeking abortion had significantly lower certainty (baseline score 28.8 and follow-up score 32.2) than those who had obtained an abortion (baseline score 21.8 and follow-up score 20.1, P<.01).

CONCLUSION:

Decision certainty is relatively high and stable over time among those who had had an abortion. Living in a state with a waiting period or two-visit requirement is not associated with increased decision certainty.
Adverse Pregnancy Outcomes Among Individuals With and Without Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)
Authors: Huntley Benjamin J. F. , Mulder Isabelle A. , Di Mascio Daniele , Vintzileos William S. , Vintzileos Anthony M. , Berghella Vincenzo , Chauhan Suneet P.
Published: March 2021

OBJECTIVE:

To compare the risk of intrauterine fetal death (20 weeks of gestation or later) and neonatal death among individuals who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) compared with those who tested negative for SARS-CoV-2 on admission for delivery.

DATA SOURCES:

MEDLINE, Ovid, EMBASE, Cumulative Index to Nursing and Allied Health, and Cochrane Library were searched from their inception until July 17, 2020. Hand search for additional articles continued through September 24, 2020. ClinicalTrials.gov was searched on October 21, 2020.

METHODS OF STUDY SELECTION:

The inclusion criteria were publications that compared at least 20 cases of both pregnant patients who tested positive for SARS-CoV-2 on admission to labor and delivery and those who tested negative. Exclusion criteria were publications with fewer than 20 individuals in either category or those lacking data on primary outcomes. A systematic search of the selected databases was performed, with co-primary outcomes being rates of intrauterine fetal death and neonatal death. Secondary outcomes included rates of maternal and neonatal adverse outcomes.

TABULATION, INTEGRATION, AND RESULTS:

Of the 941 articles and completed trials identified, six studies met criteria. Our analysis included 728 deliveries to patients who tested positive for SARS-CoV-2 and 3,836 contemporaneous deliveries to patients who tested negative. Intrauterine fetal death occurred in 8 of 728 (1.1%) patients who tested positive and 44 of 3,836 (1.1%) who tested negative (P=.60). Neonatal death occurred in 0 of 432 (0.0%) patients who tested positive and 5 of 2,400 (0.2%) who tested negative (P=.90). Preterm birth occurred in 95 of 714 (13.3%) patients who tested positive and 446 of 3,759 (11.9%) who tested negative (P=.31). Maternal death occurred in 3 of 559 (0.5%) patients who tested positive and 8 of 3,155 (0.3%) who tested negative (P=.23).

CONCLUSION:

The incidences of intrauterine fetal death and neonatal death were similar among individuals who tested positive compared with negative for SARS-CoV-2 when admitted to labor and delivery. Other immediate outcomes of the newborns were also similar among those born to individuals who tested positive compared with negative for SARS-CoV-2.

SYSTEMATIC REVIEW REGISTRATION:

PROSPERO, CRD42020203475.
Community-Engaged Curriculum Development in Sexual and Reproductive Health Equity
Authors: Julian Zoë , Mengesha Biftu , McLemore Monica R. , Steinauer Jody
Published: March 2021

BACKGROUND:

Inequitable outcomes in sexual and reproductive health disproportionately burden communities minoritized by systems of oppression. Although there is evidence linking structural determinants to these inequities, clinical learners have limited exposure to these topics in their training. We developed a curriculum aimed to teach clinical learners the structural determinants of sexual and reproductive health.

METHOD:

We implemented Kern’s six-step method for curriculum development. Through literature review, we identified structural competency as the foundational framework and explored community priorities for clinical training. We assessed learner needs regarding structural equity training, articulated goals and objectives, and chose video modules as the primary educational strategy. We collaboratively developed content with community scholars and reproductive justice advocates. For phase 1 of our curriculum, we created pillar videos with reflection questions, resources, and a visual glossary of key terms. All materials are available through an online educational platform offering open-access, evidence-based curricula.

EXPERIENCE:

We launched our curriculum with a social media campaign and presented our videos at several national convenings. We implemented videos with clinical learners with positive preliminary evaluation results.

CONCLUSION:

With rigorous development rooted in community engagement, our curriculum contributes to the tools promoting structural equity training in obstetrics and gynecology.
Racial–Ethnic Comparison of Guideline-Adherent Gynecologic Cancer Care in an Equal-Access System
Authors: Eaglehouse Yvonne L. , Darcy Kathleen M. , Tian Chunqiao , Casablanca Yovanni , Shriver Craig D. , Zhu Kangmin
Published: March 2021

OBJECTIVE:

To compare receipt of National Comprehensive Cancer Network Guideline–adherent treatment for gynecologic cancers, inclusive of uterine, cervical, and ovarian cancer, between non-Hispanic White women and racial–ethnic minority women in the equal-access Military Health System.

METHODS:

We accessed MilCanEpi, which links data from the Department of Defense Central Cancer Registry and Military Health System Data Repository administrative claims data, to identify a cohort of women aged 18–79 years who were diagnosed with uterine, cervical, or ovarian cancer between January 1, 1998, and December 31, 2014. Information on tumor stage, grade, and histology was used to determine which treatment(s) (surgery, chemotherapy, radiotherapy) was indicated for each patient according to the National Comprehensive Cancer Network Guidelines during the period of the data (1998–2014). We compared non-Hispanic Black, Asian, and Hispanic women with non-Hispanic White women in their likelihood to receive guideline-adherent treatment using multivariable logistic regression models given as adjusted odds ratios (aORs) and 95% CIs.

RESULTS:

The study included 3,354 women diagnosed with a gynecologic cancer of whom 68.7% were non-Hispanic White, 15.6% Asian, 9.0% non-Hispanic Black, and 6.7% Hispanic. Overall, 77.8% of patients received guideline-adherent treatment (79.1% non-Hispanic White, 75.9% Asian, 69.3% non-Hispanic Black, and 80.5% Hispanic). Guideline-adherent treatment was similar in Asian compared with non-Hispanic White patients (aOR 1.18, 95% CI 0.84–1.48) or Hispanic compared with non-Hispanic White women (aOR 1.30, 95% CI 0.86–1.96). Non-Hispanic Black patients were marginally less likely to receive guideline-adherent treatment compared with non-Hispanic White women (aOR 0.73, 95% CI 0.53−1.00, P=.011) and significantly less likely to receive guideline-adherent treatment than either Asian (aOR 0.65, 95% CI 0.44–0.97) or Hispanic patients (aOR 0.56, 95% CI 0.34–0.92).

CONCLUSION:

Racial–ethnic differences in guideline-adherent care among patients in the equal-access Military Health System suggest factors other than access to care contributed to the observed disparities.
Superior Hypogastric Plexus Block to Reduce Pain After Laparoscopic Hysterectomy
Authors: Clark Nisse V. , Moore Kristin , Maghsoudlou Parmida , North Alexandra , Ajao Mobolaji O. , Einarsson Jon I. , Louie Michelle , Schiff Lauren , Moawad Gaby , Cohen Sarah L. , Carey Erin T.
Published: March 2021

OBJECTIVE:

To assess whether a superior hypogastric plexus block performed during laparoscopic hysterectomy reduces postoperative pain.

METHODS:

We conducted a multicenter, randomized, single-blind, controlled trial of superior hypogastric plexus block at the start of laparoscopic hysterectomy. Women undergoing a laparoscopic hysterectomy for any indication and with any other concomitant laparoscopic procedure were eligible. Standardized preoperative medications and incisional analgesia were provided to all patients. Our primary outcome was the proportion of patients with a mean visual analog scale (VAS) pain score lower than 4 within 2 hours postoperatively. Patients but not surgeons were blinded to the treatment group. Twenty-nine patients per group was estimated to be sufficient to detect a 38% absolute difference in the proportion of patients with a VAS score lower than 4 at 2 hours postoperatively, with 80% power and an α of 0.05. To account for loss to follow-up and potential imbalances in patient characteristics, we planned to enroll 50 patients per group. All analyses were intention to treat.

RESULTS:

Between January 2018 and February 2019, 186 patients were eligible; 100 were randomized and analyzed. Demographic and clinical characteristics were similar between the two groups. There was no significant difference in the proportion of patients with a mean VAS score lower than 4 within 2 hours postoperatively between patients who received a superior hypogastric plexus block (57%) and patients who did not (43%) (odds ratio 1.63, 95% CI 0.74–3.59; adjusted odds ratio 1.84, 95% CI 0.75–4.51).

CONCLUSION:

Among patients undergoing laparoscopic hysterectomy with standardized enhanced perioperative recovery pathways, superior hypogastric plexus block did not significantly reduce postoperative pain.

CLINICAL TRIAL REGISTRATION:

ClinicalTrials.gov, NCT03283436.
Emergence of a plasmid-borne tigecycline resistance in Klebsiella pneumoniae in Vietnam
Authors: Hirabayashi Aki , Ha Van Thi Thu , Nguyen An Van , Nguyen Son Thai , Shibayama Keigo , Suzuki Masato
Published: March 2021

Tigecycline is a last-resort antimicrobial used to treat multidrug-resistant Gram-negative bacterial infections. One of the common antimicrobial resistance mechanisms is the efflux pump system composed of membrane protein complexes to excrete xenobiotic substrates. Recently, a novel gene cluster, tmexCD1-toprJ1, encoding the resistance–nodulation–cell division (RND) efflux pump was identified on plasmids in

Klebsiella pneumoniae

isolates in China. TMexCD1-TOprJ1 was found to be capable of excreting multiple antimicrobials, including tigecycline, which contributed to the strain's resistance. In this study, we identified

K. pneumoniae

isolates harbouring the tmexCD1-toprJ1 genes outside of China for the first time. Two tigecycline-resistant

K. pneumoniae

isolates belonging to ST273 by multilocus sequence typing were collected from different patients in a medical institution in Hanoi, Vietnam, in 2015. Whole-genome sequence analysis revealed that these isolates harboured a 288.0 kb tmexCD1-toprJ1–carrying plasmid with IncFIB and IncHI1B replicons. The tmexCD1-toprJ1 gene cluster was surrounded by several mobile gene elements, including IS26, and the plasmids had high sequence identity with that of

K. pneumoniae

isolated in China. Our finding suggests that the horizontal spread of tigecycline resistance mediated by tmexCD1-toprJ1–carrying plasmids has occurred in Vietnam and other countries, and raises concern about the further global dissemination.
Ethical and human subject burdens of trials conducted to evaluate biosimilars
Authors: Ohn Jennifer A. , Atteberry Preston J. , Trusheim Mark R. , Bach Peter B.
Published: March 2021

Background/Aims

With a policy goal of introducing price competition into the market for biologic drugs after their period of market monopoly is over (called ‘loss of exclusivity’), policymakers created a pathway for companies to make copies of those treatments and termed them ‘biosimilars’. But unlike generic drugs, biosimilar drug copies must be studied in human trials to assure they have the same clinical effect as the original biologic products. The burden that this places on human subject participants, and the opportunity cost on the clinical trial system generally, have not been considered in detail.

Methods

For all biosimilar drugs in development, approved, or that failed to obtain approval in the US, we abstracted from clinicaltrials.gov registry the number of subjects enrolled at each phase of development.

Results

We identified 105 clinical trials for approved or withdrawn biosimilars and another 20 studies that are either planned, ongoing or completed for biosimilars in development. These studies collectively enrolled (or plan to enroll) 38,169 human subjects. Most (28,130) are enrolled in phase 3 studies. The mean number of human subject participants per approval is 1,045, about 25% of the number required for a new drug approval on average.

Conclusions

A consequential number of human subjects are required for the testing of biosimilar drugs prior to approval. The explicit and sole purpose of biosimilars is to induce competition in order to lower prices of biologic drugs after loss of exclusivity. The burden the biosimilar approval trials place on human subjects with no direct clinical benefits but definite risks, and the possibility that they rob subjects from trials that are of more scientific importance, are ones policymakers might consider. Price regulation of biologic drugs after loss of exclusivity could achieve lower prices as well, without the burdens of the current approach.

Funding Source

Arnold Ventures (Grant to support Drug Pricing Lab at Memorial Sloan Kettering Cancer Center)
Genome-wide annotation of gene regulatory elements linked to cell fitness
Authors: Klann Tyler S. , Barrera Alejandro , Ettyreddy Adarsh R. , Rickels Ryan A. , Bryois Julien , Jiang Simon , Adkar Shaunak S. , Iglesias Nahid , Sullivan Patrick F. , Reddy Timothy E. , Crawford Gregory E. , Gersbach Charles A.
Published: March 2021

Noncoding regulatory elements control gene expression and govern all biological processes. Epigenomic profiling assays have identified millions of putative regulatory elements, but systematically determining the function of each of those regulatory elements remains a substantial challenge. Here we adapt CRISPR-dCas9-based epigenomic regulatory element screening (CERES) technology to screen all >100,000 putative non-coding regulatory elements defined by open chromatin sites in human K562 leukemia cells for their role in regulating essential cellular processes. In an initial screen containing more than 1 million gRNAs, we discovered approximately 12,000 regulatory elements with evidence of impact on cell fitness. We validated many of the screen hits in K562 cells, evaluated cell-type specificity in a second cancer cell line, and identified target genes of regulatory elements using CERES perturbations combined with single cell RNA-seq. This comprehensive and quantitative genome-wide map of essential regulatory elements represents a framework for extensive characterization of noncoding regulatory elements that drive complex cell phenotypes and for prioritizing non-coding genetic variants that likely contribute to common traits and disease risk.
Transposon-induced inversions activate gene expression in Maize pericarp
Authors: Sharma Sharu Paul , Zuo Tao , Peterson Thomas
Published: March 2021

Chromosomal inversions can have considerable biological and agronomic impacts including disrupted gene function, change in gene expression and inhibited recombination. Here we describe the molecular structure and functional impact of six inversions caused by Alternative Transpositions betweenp1andp2genes responsible for floral pigmentation in maize. In maize linep1-wwB54, thep2gene is expressed in anther and silk but not in pericarp, making the kernels white. We identified inversions in this region caused by transposition ofAcandfractured Ac(fAc) transposable elements. These inversions change the position of ap1enhancer and activate the expression ofp2in the kernel pericarp, resulting in red kernel color. We hypothesize that these inversions place thep2gene promoter near ap1gene enhancer, thereby activatingp2expression in kernel pericarp.
A tandem-repeat dimeric RBD protein-based COVID-19 vaccine ZF2001 protects mice and nonhuman primates
Authors: An Yaling , Li Shihua , Jin Xiyue , Han Jian-bao , Xu Kun , Xu Senyu , Han Yuxuan , Liu Chuanyu , Zheng Tianyi , Liu Mei , Yang Mi , Song Tian-zhang , Huang Baoying , Zhao Li , Wang Wen , Ruhan A , Cheng Yingjie , Wu Changwei , Huang Enqi , Yang Shilong , Wong Gary , Bi Yuhai , Ke Changwen , Tan Wenjie , Yan Jinghua , Zheng Yong-tang , Dai Lianpan , Gao George F.
Published: March 2021

A safe, efficacious and deployable vaccine is urgently needed to control COVID-19 pandemic. We report here the preclinical development of a COVID-19 vaccine candidate, ZF2001, which contains tandem-repeat dimeric receptor-binding domain (RBD) protein with alum-based adjuvant. We assessed vaccine immunogenicity and efficacy in both mice and non-human primates (NHPs). ZF2001 induced high levels of RBD-binding and SARS-CoV-2 neutralizing antibody in both mice and NHPs, and also elicited balanced TH1/TH2 cellular responses in NHPs. Two doses of ZF2001 protected Ad-hACE2-transduced mice against SARS-CoV-2 infection, as detected by reduced viral RNA and relieved lung injuries. In NHPs, vaccination of either 25 μg or 50 μg ZF2001 prevented infection with SARS-CoV-2 in lung, trachea and bronchi, with milder lung lesions. No evidence of disease enhancement is observed in both models. ZF2001 is being evaluated in the ongoing international multi-center Phase 3 trials (NCT04646590) and has been approved for emergency use in Uzbekistan.
Freedom and flexibility: the work–family balance of single female entrepreneurs in Nigeria
Authors: Adisa Toyin Ajibade , Mordi Chima , Akanji Babatunde
Published: March 2021

Purpose

Work–family research has mainly focused on nuclear families, neglecting other types of families, such as single self-employed parents. To what extent does the freedom and flexibility attached to being single and self-employed hinder or enhance single parents' work–family balance? Using role theory as a theoretical lens, this study examines single-self-employed parents' work–family balance.

Design/methodology/approach

Drawing on the accounts of 25 single self-employed parents in Nigeria, the article uses semi-structured interviews to examine how this group achieves work–family balance.

Findings

We found that the freedom and flexibility associated with being single and self-employed form a double-edged sword that increases the spate of singlehood and intensifies commitments to work, altogether preventing the participants in the study from achieving work–family balance. The findings also indicate that singlehood and a lack of spousal support cause and exacerbate work–family imbalance for this group. The findings further indicate that the reconstruction of functions, and the recreation of the traditional masculine gender role overwhelm single self-employed women in their entrepreneurial activities, thereby causing a lack of time and the energy required to function well in a family role, thus creating imbalance between the different spheres of life.

Research limitations/implications

The extent to which the findings of this research can be generalised is constrained by the limited sample and scope of the research.

Practical implications

While literature espouses freedom and flexibility as important ingredients needed to achieve work–family balance, this study shows that they enhance inter-role role conflict. The study suggests creation of private or family time, devoid of work or entrepreneurial engagements, for single female entrepreneurs. This will ensure quality time and energy for the family and for fresh relationship – all of which will impact business positively.

Originality/value

Rather than enhancing work–family balance, the freedom and flexibility attached to being single and self-employed remain the main source of work–family imbalance for Nigerian single self-employed parents.