bluuebunny/crossref_metadata_2025 huggingface dataset:
Trends in Gestational Diabetes at First Live Birth by Race and Ethnicity in the US, 2011-2019
Authors: Shah N.S. , Wang M.C. , Freaney P.M. , Perak A.M. , Carnethon M.R. , Kandula N.R. , Gunderson E.P. , Bullard K.M. , Grobman W.A. , O'Brien M.J. , Khan S.S.
Published: June 2022

(JAMA. 2021;326:660–669)

Gestational diabetes mellitus (GDM) is a common condition during pregnancy associated with adverse maternal and child outcomes, including increased risk for future diabetes postpregnancy and cardiovascular disease. For infants, maternal GDM is shown to be associated with macrosomia and increased adiposity, and increased risk for cardiometabolic disease into the full lifespan. Differentiated rates of GDM in the United States has been estimated for major ethnic groups but is undefined for disaggregated subgroups within these larger populations. Large-scale data were mined to quantify annual rates of GDM in mothers at first live birth stratified across race and ethnicity subgroups in the United States. This analysis informs equitable approaches for management and prevention of gestational diabetes at the clinical and population levels.
Incidence of Subdural Catheter Placement During Epidural Procedure Based on Fluoroscopic Imaging
Authors: Sidash S. , Zhang X. , Herrick M. , McIntyre J.J. , Sites B.D.
Published: June 2022

(Reg Anesth Pain Med. 2021;46:538–539)

The percentage of failed epidural anesthesia placement due to subdural catheter placement is unknown. Subdural catheter placement is difficult to identify because it can occur despite having a negative test dose and negative aspiration of cerebrospinal fluid. This poses a problem to the patient because subdural placement may not penetrate anterior nerve roots, resulting in continued pain. This study utilized real-time fluoroscopic imaging in an effort to determine the incidence of subdural catheter placement during epidural anesthesia.
Evaluation of Therapies for Peripheral and Neuraxial Opioid-induced Pruritus based on Molecular and Cellular Discoveries
Authors: Nguyen E. , Lim G. , Ross S.E.
Published: June 2022

(Anesthesiology. 2021;135:350–365)

The clinical burden of opioid-induced pruritus is observed in many patient populations. Opioids are used to control numerous types of pain including acute, chronic, preoperative, intraoperative and postoperative, and cancer pain. Pruritus is an extremely common side effect of neuraxial opioids (30% to 85%) and also occurs with parenteral administration particularly after extended dosing. Pruritis secondary to neuraxial opioids in the childbirth setting is also extremely common (up to 85%) and is primarily dose dependent. Pruritus following neuraxial opioid administration is more common in women in all settings (60% to 85%), mirroring the elevated incidence of chronic pain that also affects female patients, perhaps implicating sensitivities of the μ-opioid receptor susceptible to the estrous cycle. Polymorphisms of the human μ-opioid receptor (OPRM1) may be associated with protection against the effects of pruritus.
Maternal Vitamin D, Oxidative Stress, and Preeclampsia
Authors: Wei S.Q. , Bilodeau J.-F. , Julien P. , Luo Z.-C. , Abenhaim H.A. , Bi W.G. , Nuyt A.M. , Leduc L. , Audibert F. , Fraser W.D.
Published: June 2022

(Int J Gynecol Obstet. 2021;154:444–450)

Preeclampsia (PE) is a serious and complex pregnancy-related disorder with negative effects on both the mother and fetus. Prevention is vital to reduce 18% of maternal mortality that results from PE in the United States each year. After years of study, its causes and mechanisms have not yet been fully unraveled. A recent review and analysis have shown an association between maternal vitamin D levels during pregnancy and an increased risk of PE.
COVID-19 Vaccine Acceptance in Pregnant Women
Authors: Ayhan S.G. , Oluklu D. , Atalay A. , Beser D.M. , Tanacan A. , Tekin O.M. , Sahin D.
Published: June 2022

(Int J Gynecol Obstet. 2021;154:291–296)

In the time since the SARS-CoV-2 pandemic began in 2020, over 5 million deaths worldwide have been attributed to the disease, COVID-19, which the SARS-COV-2 virus causes. Pregnant women who contract COVID-19 have been shown in studies to be 20 times more likely to die of complications from the disease than their pregnant peers who do not contract COVID-19. Infected pregnant women are much more likely to develop preeclampsia, experience preterm birth, require intubation, and stay in an ICU setting. They are at higher risk for severe disease than both their noninfected pregnant peers and their nonpregnant infected peers. Although new treatments for COVID-19 are emerging, the best way for pregnant women to protect themselves and their unborn baby from the effects of COVID-19 is through vaccination. Vaccination for COVID-19 has been shown to strengthen an individual’s immune response and decrease the severity of the disease in infected individuals.
The FAST-M Complex Intervention for the Detection and Management of Maternal Sepsis in Low-resource Settings: A Multi-site Evaluation
Authors: Cheshire J. , Jones L. , Munthali L. , Kamphinga C. , Liyaya H. , Phiri T. , Parry-Smith W. , Dunlop C. , Makwenda C. , Devall A.J. , Tobias A. , Nambiar B. , Merriel A. , Williams H.M. , Gallos I. , Wilson A. , Coomarasamy A. , Lissauer D.
Published: June 2022

(BJOG. 2021;128:1324–1333)

Maternal sepsis is the third most common direct cause of maternal mortality worldwide. Low-resource settings are disproportionately affected by maternal sepsis. While sepsis screening and care bundles can reduce the time to initiation of treatment and improve outcomes, the current bundles are not specific to maternal care nor are they suitable for low-resource settings. The FAST-M maternal sepsis care bundle was developed using a modified Delphi process with input from care providers from low- to middle-income countries. This study aimed to gauge the feasibility of implementing the FAST-M complex intervention in low-resource settings.
Magnetic Resonance Imaging of Cerebrospinal Fluid Spread in the Epidural Space and Postdural Puncture Headache in Obstetrics: A Proof-of-Concept Study
Authors: Ahmed I. , Majeed A. , Fernando R. , Hyare H. , Columb M. , Setty T.
Published: June 2022

(Eur J Anaesthesiol. 2021;38:777–784)

Labor analgesia that includes epidural catheter placement can be complicated by accidental dural puncture (ADP). In parturients, ADP is followed by postdural puncture headache (PDPH) in up to 70% to 80% of cases. Prompt diagnosis and treatment of PDPH are important as delay can exacerbate sequelae, leading to serious debilitating and chronic complications. The current most effective treatment, epidural blood patch (EBP), is performed based on subjective clinical judgment of the parturient’s progression and severity of symptoms. An evidence-based protocol may benefit parturients with atypical PDPH presentation by allowing an earlier EBP, rather than forestalling until PDPH becomes severe. Egress of cerebrospinal fluid (CSF) into the epidural space following ADP can be readily recognized in T1-weighted and T2-weighted magnetic resonance imaging (MRI) of the brain and spine. The correlations between neuroradiological findings and the severity of PDPH in obstetric patients is presented.
Optimal Use of Intravenous Tranexamic Acid for Hemorrhage Prevention in Pregnant Women
Authors: Ahmadzia H.K. , Luban N.L.C. , Li S. , Guo D. , Miszta A. , Gobburu J.V.S. , Berger J.S. , James A.H. , Wolberg A.S. , van den Anker J.
Published: June 2022

(Am J Obstet Gynecol. 2021;225:85.e1–11)

Postpartum hemorrhage (PPH) is a major cause of pregnancy-related death worldwide. Tranexamic acid (TXA) reduced death from bleeding by 31% when administered to women with PPH in the World Maternal Antifibrinolytic (WOMAN) trial. While some data suggests a low dose of TXA may achieve a therapeutic effect while minimizing exposure to the neonate, there is a lack of data on the use of TXA in pregnant women, including pharmacokinetic (PK) and pharmacodynamic (PD) data. This study aimed to evaluate the safety of using TXA in women undergoing cesarean delivery, including PK and PD outcomes, and to provide data on breast milk TXA concentration.
Pregnancy-related Venous Thromboembolism and HIV Infection
Authors: Schapkaitz E. , Libhaber E. , Rhemtula H. , Gerber A. , Jacobson B.F. , Chauke L. , Buller H.R.
Published: June 2022

(Int J Gynecol Obstet. 2021;155:110–118)

Pregnant women and recently pregnant women are at an increased risk for venous blood clots due to pregnancy being an acquired hyper-coagulable state. This state is caused by increased platelet activation, a reduction in free and total proteins, and decreased fibrinolysis. The increase in thrombin predisposes pregnant women to venous thromboembolism (VTE) which can lead to deep vein thrombosis and pulmonary embolism. Conditions which can increase a mother’s likelihood for VTE include a personal history of thrombosis, inherited thrombophilia, medical comorbidities, age above 35, significant pregnancy complications, and especially cesarean delivery.
Surgical, Obstetric, and Anesthetic Mortality Measurement at a Ugandan Secondary Referral Hospital
Authors: Firth P.G. , Mushagara R. , Musinguzi N. , Liu C. , Boatin A.A. , Mugabi W. , Kayaga D. , Naturinda P. , Twesigye D. , Sanyu F. , Mugyenyi G. , Ngonzi J. , Ttendo S.S.
Published: June 2022

(Anesth Analg. 2021;133:1608–1616)

In low- and middle-income countries, health care systems may have limited ability to safely treat surgical disorders. An appropriate standardized metric is needed to assess hospital and patient outcomes in terms of safe surgical care in low-income countries. The perioperative mortality rate (POMR) is one metric used to compare the quality and safety of hospitals in high- and low-income countries. In Uganda, the Mbarara Regional Referral Hospital (MRRH) is a government-funded hospital located in a rural area. This study examined surgical deaths over one year at this hospital with the aim of determining a suitable mortality metric to measure outcomes and assess care delivery in this limited-resource health system. The hypothesis was that the majority of admission deaths did not involve an operation.
The Extension of Epidural Blockade for Emergency Cesarean Delivery: A Survey of UK Practice
Authors: Richardson A.L. , Bhuptani S. , Lucas D.N.
Published: June 2022

(Int J Obstet Anesth. 2021;46:102977)

One-fifth of emergency cesarean deliveries (CD) in the United Kingdom are performed under extension of labor epidural analgesia to surgical anesthesia. In 2014, a survey was sent to lead obstetric anesthetists in the United Kingdom regarding practices for extending labor analgesia to achieve surgical anesthesia. These results were compared with a similar survey published in 2008.
Technical Trick: T-Bar External Fixator for Definitive Management of Periarticular and Metadiaphyseal Tibial Fractures
Authors: Mease Samuel J. , Bradley Hallie R. , Thota Dharani R. , Starr Adam J. , Sanders Drew T.
Published: June 2022

Purpose:

Tibia fractures with soft tissue compromise present are challenging to manage. For fractures with significant swelling or open injury not amenable to internal stabilization, external fixators provide sufficient stability for bony healing. Ring fixators and hybrid constructs provide adequate stability for healing but are costly, and challenging to apply and maintain. We present the “T-bar” external fixator, a novel construct that can be maintained until bony union and allows for range of motion of adjacent joints. We also report the demographics, clinical, and radiographic outcomes of 34 patients treated definitively with this construct.

Materials and Methods:

The T-bar external fixator uses standard pins and bars in a novel arrangement. It can be applied for Arbeitsgemeinshaft fur Osteosynthesefragen/Orthopaedic Trauma Association-type 41/42/43 type injuries, with or without supplemental fixation for intra-articular patterns.

Results:

Between 2008 and 2015, 34 patients were treated for tibia fracture with T-bar external fixation, with intention to treat in a definitive manner. Twenty-nine were male, and average age was 44.3 years. Thirty-one sustained high energy mechanisms of injury. Twenty were Gustilo-type 2 or 3 fractures. Of 14 closed fractures, 12 were Tscherne-type 2 or 3.

Conclusions:

The T-bar external fixator offers an alternative to ring and hybrid external fixator constructs in treatment of tibia fractures with significant soft tissue compromise. Of 28 patients with complete follow up, only 1 case of osteomyelitis was reported. All patients were managed without amputation. Three required revision for nonunion, all Arbeitsgemeinshaft fur Osteosynthesefragen/Orthopaedic Trauma Association-type 43.
Advances in the treatment of gastroenteropancreatic neuroendocrine neoplasms with somatostatin analogs
Authors: Lu Ming , Zhang Panpan , Zhang Jianwei , Li Jie
Published: June 2022

Neuroendocrine neoplasms (NENs) include well-differentiated neuroendocrine tumors (NETs) and poorly differentiated neuroendocrine carcinomas (NECs). Somatostatin receptors (SSTRs) are highly expressed on NETs cells, and somatostatin analogs (SSAs) could bind to SSTRs with high affinities, regulating cell proliferation and hormone secretion. As many clinical trials have demonstrated the antiproliferative efficacy and safety of SSAs in metastatic gastroenteropancreatic NETs (GEP-NETs), SSAs have been recommended by multiple NEN guidelines as the first-line therapy of GEP-NETs. In recent years, more and more researches have been exploring new therapeutic possibilities of SSA in GEP-NETs, such as high-dose SSA as second-line therapy, SSA in metastatic GEP-NETs with Ki-67 > 10%, SSA as adjuvant therapy for postoperative pancreatic NETs patients, and combinations of SSA with chemotherapy or targeted therapy. In this review, we summarized the latest published or released researches and discussed new application attempts of SSA in GEP-NETs.
Using Administrative Data to Examine Telemedicine Usage Among Medicaid Beneficiaries During the Coronavirus Disease 2019 Pandemic
Authors: Hossain Mallick , Dean Emma B. , Kaliski Daniel
Published: June 2022

Background:

The coronavirus disease 2019 (COVID-19) pandemic necessitated the replacement of in-person physician consultations with telemedicine. During the pandemic, Medicaid covered the cost of telemedicine visits.

Objectives:

The aim was to measure the adoption of telemedicine during the pandemic. We focus on key patient subgroups including those with chronic conditions, those living in urban versus rural areas, and different age groups.

Methods:

This study examined the universe of claims made by Florida Medicaid beneficiaries (n=2.4 million) between January 2019 and July 2020. Outpatient visits were identified as in-person or telemedicine. Telemedicine visits were classified into audio-visual or audio-only visits.

Results:

We find that telemedicine offsets much of the decline in in-person outpatient visits among Florida’s Medicaid enrollees, however, uptake differs by enrollee type. High utilizers of care and beneficiaries with chronic conditions were significantly more likely to use telemedicine, while enrollees living in rural areas and health professional shortage areas were moderately less likely to use telemedicine. Elderly Medicaid recipients (dual-eligibles) used audio-only telemedicine visits at higher rates than other age groups, and the demand for these consultations is more persistent.

Conclusions:

Telemedicine offset the decline in health care utilization among Florida’s Medicaid-enrolled population during the novel coronavirus pandemic, with particularly high uptake among those with prior histories of high utilization. Audio-only visits are a potentially important method of delivery for the oldest Medicaid beneficiaries.
Accommodation Is Decreased in Eyes with Acute Central Serous Chorioretinopathy
Authors: Maltsev Dmitrii S. , Kulikov Alexei N. , Vasiliev Alexander S. , Chhablani Jay
Published: June 2022

SIGNIFICANCE

This is a case-control study showing changes in accommodation in eyes with acute central serous chorioretinopathy. We found that decreased accommodative amplitude in the affected eyes may indicate suppression of parasympathetic activity in those eyes as one of the pathophysiological mechanisms controlling choroidal thickness and perfusion.

PURPOSE

This study aimed to evaluate the changes of accommodation in patients with acute central serous chorioretinopathy.

METHODS

Patients with unilateral central serous chorioretinopathy, with and without foveal involvement, as well as patients after resolution of subretinal fluid and healthy age-matched controls were included. Accommodative amplitude was measured and compared between eyes with active or resolved central serous chorioretinopathy, fellow eyes of active central serous chorioretinopathy individuals, and eyes of controls. Correlation between accommodative amplitude and ocular and demographic parameters was calculated.

RESULTS

Nineteen acute central serous chorioretinopathy patients (16 males and 3 females, 38.1 ± 5.1 years) and 17 age-matched controls (13 males and 4 females, 37.2 ± 5.4 years) were included. Accommodative amplitude in the study eyes of central serous chorioretinopathy patients was lower than that in the fellow unaffected eyes (1.25 ± 1.0 and 2.54 ± 0.94 D, respectively; P = .002) or in the eyes of healthy controls (2.41 ± 1.38 D, P = .002). In central serous chorioretinopathy eyes, after resolution of subretinal fluid or without foveal involvement, the median accommodative amplitude was lower than that in fellow eyes (1.6 [95% confidence interval, 0.83 to 1.75] and 2.7 D [95% confidence interval, 1.23 to 3.61], respectively; P = .004). No correlation was found between accommodative amplitude in affected central serous chorioretinopathy eyes and different parameters, except for age (r = −0.47, P = .04).

CONCLUSIONS

Acute central serous chorioretinopathy is associated with a substantial reduction of accommodative amplitude.
Lessons and Insights From the Implementation of the Cohort Model for a PICU: A Case Study Research
Authors: Ninemire Margaret R. , Petrescu Matei , Musick Matthew A. , Shekerdemian Lara S. , Kumar Shelley , Dinh Julie , Thammasitboon Satid
Published: June 2022

Objectives:

The subspecialty cohort model allows for creation of smaller diagnosis pools, enabling concentration of expertise and collaboration. Given unknown effects of this model on team dynamics in a PICU, we examined how the cohort-model implementation was perceived by our providers and how this organizational change affected the work environment.

Design:

Case study research approach consisting of surveys, operational observations, and semistructured interviews. A descriptive survey was derived from an integrated conceptual framework (i.e., teamwork and psychologic safety). Sensitized by the framework and quantitative survey data, we conducted a thematic analysis from field notes and interview data.

Setting:

A quaternary-care, children’s hospital with a 31-bed PICU.

Subjects:

PICU providers and nurses and subspecialists.

Intervention:

Implementation of the subspecialty cohort model.

Measurements and Main Results:

A total of 308 and 269 responses from pre- and postcohort surveys, respectively, were analyzed. Overall, 76% of physicians and 74% of nurses viewed the cohort model favorably. Three themes emerged: community-from disruption to redistribution, transforming identity-expert or generalist, and expansive learning from focused practice. The findings provided insights, informed by a theory of “Community of Practice,” as lessons learned and ways to enhance the cohort model.

Conclusions:

Our transition to a cohort PICU model offers lessons on impacts of PICU model changes on communities and teams. These theory-informed insights and implications can guide others undergoing similar transitions.
Xanthomonas bonasiae sp. nov. and Xanthomonas youngii sp. nov., isolated from crown gall tissues
Authors: Mafakheri Hamzeh , Taghavi S. Mohsen , Zarei Sadegh , Portier Perrine , Dimkić Ivica , Koebnik Ralf , Kuzmanović Nemanja , Osdaghi Ebrahim
Published: June 2022

The genus

Xanthomonas

contains a set of diverse bacterial strains, most of which are known for their pathogenicity on annual crops and fruit trees causing economically important plant diseases. Recently, five

Xanthomonas

strains were isolated from

Agrobacterium

-induced crown gall tissues of amaranth (Amaranthus sp.) and weeping fig (Ficus benjamina) plants in Iran. Phenotypic characteristics (i.e. biochemical tests and pathogenicity features) and whole genome sequence-based core-genome phylogeny followed by average nucleotide identity and digital DNA–DNA hybridization calculations suggested that these gall-associated strains belong to two new species within the genus

Xanthomonas

. In this study, we provide a formal species description for these new species where Xanthomonas bonasiae sp. nov. is proposed for the strains isolated from weeping fig with FX4T (=CFBP 8703T=DSM 112530T) as type strain. The name Xanthomonas youngii sp. nov. is proposed for the strains isolated from amaranth with AmX2T (=CFBP 8902T=DSM 112529T) as type strain.
Chromosome-level genome assembly of Rorippa aquatica revealed its allotetraploid origin and mechanisms of heterophylly upon submergence
Authors: Sakamoto Tomoaki , Ikematsu Shuka , Nakayama Hokuto , Mandáková Terezie , Gohari Gholamreza , Sakamoto Takuya , Li Gaojie , Hou Hongwei , Matsunaga Sachihiro , Lysak Martin A. , Kimura Seisuke
Published: June 2022

The ability to respond to environmental variability is essential for living systems, especially to sessile organisms such as plants. The amphibious plant Rorippa aquatica exhibits a drastic type of phenotypic plasticity known as heterophylly, a phenomenon where leaf form is altered in response to the surrounding environment. Although heterophylly has been studied in various plant species, its molecular mechanism has not been fully elucidated. To establish the genetic basis and analyze the evolutionary processes responsible for heterophylly, we assembled the chromosome-level genome of R. aquatica by combining data from Illumina short-read sequencing, PacBio long-read sequencing, and High-throughput Chromosome Conformation Capture (Hi-C) sequencing technologies. Fine-scale comparative chromosome painting and chromosomal genomics revealed that allopolyploidization and subsequent post-polyploid descending dysploidy occurred during R. aquatica speciation. The genomic information above was the basis for the transcriptome analyses to examine the mechanisms involved in heterophylly, especially in response to the submerged condition, which uncovered that the ethylene and blue light signaling pathways participate in regulating heterophylly under submerged conditions. The assembled R. aquatica reference genome provides novel insights into the molecular mechanisms and evolution of heterophylly.
Colour vision is aligned with natural scene statistics at 4 months of age
Authors: Skelton Alice E. , Franklin Anna , Bosten Jenny M.
Published: June 2022

Visual perception in adult humans is thought to be optimised to represent the statistical regularities of natural scenes (Parraga et al., 2000; Simoncelli, 2003). For example, in adults, visual sensitivity to different hues shows an asymmetry which coincides with the statistical regularities of colour in the natural world (Bosten et al., 2015). Infants are sensitive to statistical regularities in social and linguistic stimuli, but whether or not infants’ visual systems are tuned to natural scene statistics is currently unclear. We measured colour discrimination in infants to investigate whether or not the visual system can represent chromatic scene statistics in very early life. Our results reveal the earliest association between vision and natural scene statistics that has yet been found: even as young as four months of age, colour vision is aligned with the distributions of colours in natural scenes.

Research Highlights

We find infants’ hue sensitivity is aligned with the distribution of colours in the natural world, as it is in adults

At just 4 months, infants’ visual systems are tailored to extract and represent the statistical regularities of the natural world

This points to a drive for the human brain to represent statistical regularities even at a young age.
Trends and determinants of unmet need for modern contraception among adolescent girls and young women in Tanzania, 2004-2016
Authors: Kagoye Sophia Adam , Jahanpour Ola , Obure Joseph , Mahande Michael Johnson , Renju Jenny
Published: June 2022

Background

Unintended pregnancy at a young age can lead to poor reproductive health, social and economic outcomes. The high rate of unintended teenage pregnancies in Tanzania is indicative of inadequate availability and uptake of modern contraception. Determining trends and determinants of unmet need for modern contraception among adolescent girls and young women (AGYW) in Tanzania will help address the burden of unintended pregnancies.

Methodology

An analytical cross-sectional study design was conducted using secondary data from three consecutive Tanzania Demographic and Health Surveys (TDHS) 2004/05, 2010 and 2015/6. Data analysis was performed using Stata version 15.0. Data analysis considered the complex survey design. Categorical and continuous variables were summarized using descriptive statistics. Poisson regression model was used to determine factors associated with unmet need for modern contraception.

Results

A steady decline in unmet need for modern contraception was observed from 31.8% in 2004/05 to 27.5% in 2015/16 survey. In the multivariable analysis, higher prevalence of unmet need for modern contraception was observed among adolescents, participants with at least one live birth, from poor wealth tertile, and those sexually active during the past four weeks.

Conclusion

Despite declining levels, the unmet need for modern contraception among young women in Tanzania remains high. AGYW under 19 years, those from poor households, and those who are postpartum are most at risk. Greater efforts are required to meet the reproductive health needs and rights of these sub-groups of AGYW in order to facilitate uptake of modern contraceptives and therefore reducing the risk of unintended pregnancies and unmet need for modern contraception.
Proteomics for the discovery of clinical delirium biomarkers: A systematic review of Major Studies
Authors: Wiredu Kwame , Aduse-Poku Edmund , Shaefi Shahzad , Gerber Scott A
Published: June 2022

Delirium represents a significant healthcare burden, diagnosed in over two million elderly Americans each year. In the surgical population, delirium remains the most common complication among elderly patients and is associated with longer hospital stays, higher costs of care, increased mortality and functional impairment. The pathomechanism of disease is poorly understood, with current diagnostic approaches somewhat subjective and arbitrary, and definitive diagnostic biomarkers are currently lacking. Despite the recent interest in delirium research, biomarker discovery for it remains new. Most attempts to discover biomarkers are targeted studies that seek to assess the involvement of one or more members of a focused panel of candidates in delirium. For a more unbiased, systems-biology view, we searched literature from MEDLINE, Cochrane Central, Web of Science, SCOPUS, and Dimensions between 2016 and 2021 for untargeted proteomic discovery studies for biomarkers of delirium conducted on human geriatric subjects. Two reviewers conducted independent review of all search results, and resolved discordance by concensus. From an overall search of 1172 publications, eight peer-reviewed studies met our defined inclusion criteria. The 370 unique peri-operative biomarkers identified in these reports are enriched in pathways involving the activation of the immune system, inflammatory response, and the coagulation cascade. IL-6 was the most commonly identified biomarker. By reviewing the distribution of protein biomarker candidates from these studies, we conclude that a panel of proteins, rather than a single biomarker, would allow for discriminating delirium cases from non-cases. The paucity of hypothesis-generating studies in the peer-reviewed literature also suggests that a systems-biology view of delirium pathomechanisms has yet to fully emerge.
Bidirectional changes in excitability upon loss of both CAMK2A and CAMK2B
Authors: Kool Martijn J. , Bodde Hanna E. , Elgersma Ype , van Woerden Geeske M.
Published: June 2022

The mammalian Ca2+/calmodulin-dependent protein kinase II (CAMK2) family consists of 4 different CAMK2 genes, encoding CAMK2A, CAMK2B, CAMK2D and CAMK2G, which have high structural homology. CAMK2A and CAMK2B are abundantly expressed in the brain; they play a unique role in proper neuronal functioning, since both CAMK2A and CAMK2B knockout mice show several behavioural and cellular phenotypes. However, our recent finding that deletion of both CAMK2A and CAMK2B is lethal indicates that they show redundancy and that the full spectrum of CAMK2 function in neurons remains to be uncovered. For example, it still remains unclear which overlapping functions are present at a single cell level in neuronal transmission and excitability.

In order to get more insight into the full spectrum of CAMK2 functions in neurons, we performed whole-cell patch clamp experiments in inducible Camk2a/Camk2b double knockout mice, as well as the CAMK2A and CAMK2B knockout mice. We found that whereas deletion of only CAMK2A or CAMK2B did not change excitability, simultaneous deletion of CAMK2A and CAMK2B resulted in a decrease in excitability 10 days after deletion in CA1 pyramidal neurons, which reversed to increased excitability 21 days after deletion. Additionally, loss of both CAMK2A and CAMK2B resulted in a decreased frequency of both miniature excitatory and inhibitory postsynaptic currents (mEPSC and mIPSC) 21 days after deletion, but not 10 days after deletion, an effect not seen in the single mutants. Our results indicate that CAMK2 is critically important to maintain normal excitability of hippocampal CA1 pyramidal cells, as well as normal inhibitory and excitatory synaptic transmission. Together, these results lead to new insights in how CAMK2 regulates normal neuronal function and highlight the importance of having both CAMK2A and CAMK2B expressed in high levels in the brain.
A mechanistic understanding of biofilm morphogenesis: Coexistence of mobile and sessile aggregates and phase-separated patterns
Authors: Bera Palash , Wasim Abdul , Ghosh Pushpita
Published: June 2022

Most bacteria in the natural environment self-organize into collective phases such as cell clusters, swarms, patterned colonies, or biofilms. The occurrence of different phases and their coexistence is governed by several intrinsic and extrinsic factors such as the growth, motion, and physicochemical interactions. Hence, it is crucial to predict the conditions under which a collective phase emerges due to the individual-level interactions. Here we develop a particle-based biophyiscal model of bacterial cells and self-secreted extracellular polymeric substances (EPS) to decipher the interplay of growth, motility-mediated dispersal, and mechanical interactions during microcolony morphogenesis. We show that depending upon the heterogeneous production and physicochemical properties of EPS, whether sticky or nonadsorbing in nature, the microcolony dynamics and architecture significantly varies. In particular, in sticky EPS, microcolony shows the coexistence of both motile and sessile aggregates rendering a transition towards biofilm formation. Wherein for the nonad-sorbing EPS, which behaves as depletant in the media, a variety of phase-segregated patterned colonies either localizing the matrix component or cells at the colony periphery may emerge. We identified that the interplay of differential dispersion and the mechanical interactions among the components of the colony determines the fate of the colony morphology. Our results provide a significant understanding of the mechano-self-regulation during biofilm morphogenesis and open up possibilities of designing experiments to test the predictions.
Planktonic functional diversity changes in synchrony with lake ecosystem state
Authors: O’Brien Duncan A. , Gal Gideon , Thackeray Stephen J. , Matsuzaki Shin-ichiro S. , Blanchard Julia L. , Clements Christopher F.
Published: June 2022

Managing ecosystems to effectively preserve function and services requires reliable tools that can infer changes in the stability and dynamics of a system. Conceptually, functional diversity (FD) appears a viable monitoring metric due to its mechanistic influence on ecological processes, but it is unclear whether changes in FD occur prior to state responses or vice versa. We examine the lagged relationship between planktonic FD and abundance-based metrics of system state (e.g. biomass) across five highly monitored lake communities using both correlation and non-linear causality approaches. Overall, phytoplankton and zooplankton FD display synchrony with lake state but each lake is idiosyncratic in the strength of relationship. It is therefore unlikely that changes in plankton FD are identifiable before changes in more easily collected abundance metrics. This suggests that FD is unlikely to be a viable early indicator, but has value as an alternative state measure if considered at the lake level.

Graphical Abstract

Data accessibility statement:

Lake Kinneret and Lake Kasumigaura data are available on request, with all other data publicly available and referenced throughout. All code for analysis is available in the Zenodo record (to be released) and the associated GitHub repository (https://github.com/duncanobrien/plankton-FD).
Quantitative trait locus mapping of osmotic stress response in the fungal wheat pathogenZymoseptoria tritici
Authors: Stapley Jessica , McDonald Bruce A.
Published: June 2022

Osmotic stress is a ubiquitous and potent stress for all living organisms, but few studies have investigated the genetic basis of salt tolerance in filamentous fungi. The main aim of this study was to identify regions of the genome associated with tolerance to potassium chloride in the wheat pathogenZymoseptoria tritici.A secondary aim was to identify candidate genes affecting salt tolerance within the most promising chromosomal regions. We achieved these aims with a quantitative trait locus (QTL) mapping study using offspring from two crosses grown in vitro in the presence or absence of osmotic stress imposed by 0.75M KCl. We identified significant QTL for most of the traits in both crosses. Several QTL overlapped with QTL identified in earlier studies for other traits and some QTL explained trait variation in both the control and salt stress environments. A significant QTL on chromosome 3 explained variation in colony radius at 8 days post inoculation (dpi) in the KCl environment as well as colony radius KCl tolerance at 8 dpi. The QTL peak had a high LOD and encompassed an interval containing only 36 genes. Six of these genes present promising candidates for functional analyses. A GO enrichment analysis of QTL unique to the KCl environment found evidence for enrichment of functions involved in osmotic stress responses.
The Arabidopsis D27-like1 is a cis/cis/trans-β-carotene Isomerase that Contributes to Strigolactone Biosynthesis and Negatively Impacts Abscisic Acid Level
Authors: Yang Yu , Abuauf Haneen , Song Shanshan , Wang Jian You , Alagoz Yagiz , Moreno Juan C. , Mi Jianing , Ablazov Abdugaffor , Jamil Muhammad , Ali Shawkat , Zheng Xiongjie , Balakrishna Aparna , Blilou Ikram , Al-Babili Salim
Published: June 2022

The enzyme DWARF27 (D27) catalyzes the reversible isomerization of all-trans- into 9-cis-β-carotene, initiating strigolactone (SL) biosynthesis. Genomes of higher plants encode two D27-homologs, D27-like1 and -like2, with unknown functions. Here, we investigated the enzymatic activity and biological function of the Arabidopsis D27-like1. In vitro enzymatic assays and Expression in Synechocystis sp. PCC6803 revealed a yet not reported 13-cis/15-cis/9-cis- and a 9-cis/all-trans-β-carotene isomerization. Although disruption of AtD27-like1 did not cause SL deficiency phenotypes, overexpression of AtD27-like1 in the Atd27 mutant restored the more-branching phenotype, indicating a contribution of AtD27-like1 to SL biosynthesis. Accordingly, generated Atd27 Atd27like1 double mutants showed more pronounced branching phenotype, compared to Atd27. The contribution of AtD27-like1 to SL biosynthesis is likely due to its formation of 9-cis-β-carotene that was present at higher levels in AtD27-like1 overexpressing lines. In contrast, AtD27-like1 expression correlated negatively with the content of 9-cis-violaxanthin, a precursor of abscisic acid (ABA), in shoots. Consistently, ABA levels were higher in shoots and also in dry seeds of the Atd27like1 and Atd27 Atd27like1 mutants. Transgenic lines expressing β-glucuronidase (GUS) driven by the AtD27LIKE1 promoter and transcript analysis performed with hormone-treated Arabidopsis seedlings unraveled that AtD27LIKE1 is expressed in different tissues and regulated ABA and auxin. Taken together, our work revealed a cis/cis-β-carotene isomerase activity that affects the content of both cis-carotenoid derived plant hormones ABA and SLs.
Excessive Mechanotransduction in Sensory Neurons Causes Joint Contractures in a Mouse Model of Arthrogryposis
Authors: Ma Shang , Dubin Adrienne E. , Romero Luis O. , Loud Meaghan , Salazar Alexandra , Wang Yu , Chesler Alex T. , Wilkinson Katherine , Vásquez Valeria , Marshall Kara L. , Patapoutian Ardem
Published: June 2022

Distal arthrogryposis (DA) is a collection of rare disorders characterized by congenital joint contractures. Most DA mutations are in muscle- and joint-related genes, and the anatomical defects originate cell-autonomously within the musculoskeletal system. However, gain-of-function (GOF) mutations in PIEZO2, a principal mechanosensor in somatosensation, cause DA subtype 5 via unknown mechanisms. We show that expression of a GOF PIEZO2 mutation in proprioceptive sensory neurons mainly innervating muscle spindles and tendons is sufficient to induce DA5-like phenotypes in mice. Overactive PIEZO2 causes anatomical defects via increased activity within the peripheral nervous system during postnatal development. Remarkably, Botox and a dietary fatty acid that modulates PIEZO2 activity markedly reduce DA5-like deficits. This reveals an unexpected role for somatosensory neurons: excessive mechanosensation within these neurons disrupts musculoskeletal development.
Mouse tissue harvest-induced hypoxia rapidly alters the in vivo metabolome, between-genotype metabolite level differences, and 13C-tracing enrichments
Authors: Rauckhorst Adam J. , Borcherding Nicholas , Pape Daniel J. , Kraus Alora S. , Scerbo Diego A. , Taylor Eric B.
Published: June 2022

Metabolism is potently regulated by oxygen as the terminal acceptor of the electron transport chain. Thus, a challenge for capturing the in vivo metabolome of animal tissues is to achieve rapid freezing after dissection-induced loss of perfusion before the onset of hypoxia-driven metabolomic remodeling. However, the timing of the metabolomic changes elicited by post-dissection freezing delays are not well described. We addressed this problem by carefully and systematically assessing broad, genotype-specific, and 13C isotopologue metabolomic change resulting from post-dissection, ex vivo mouse tissue metabolism. Based on experiments with mouse liver, heart muscle, and skeletal muscle, we show that broad metabolomic change is rapid, that both false negative and false positive between genotype differences are induced, and that 13C-isotopologue abundances and enrichment percentages change with post-dissection hypoxia. These findings provide a previously absent, systematic illustration of the extensive and confounding metabolomic changes occurring within the early minutes of delayed tissue freezing.
Serotype specific sugars impact structure but not functions of the trimeric autotransporter adhesin EmaA of Aggregatibacter actinomycetemcomitans
Authors: Tang-Siegel Gaoyan G. , Radermacher Michael , Mintz Keith P. , Ruiz Teresa
Published: June 2022

The human oral pathobiont Aggregatibacter actinomycetemcomitans expresses multiple virulence factors including the trimeric, extracellular matrix protein adhesin A (EmaA). The posttranslational modification of EmaA is proposed to be dependent on the sugars and enzymes associated with O-polysaccharide (O-PS) synthesis of the lipopolysaccharide (LPS). This modification is important for the structure and function of this adhesin. To determine if the composition of the sugars alters structure and/or function, the prototypic 202 kDa protein was expressed in a non-serotype b, emaA mutant strain. The transformed strain displayed EmaA adhesins similar in appearance to the prototypic adhesin as observed by 2D electron microscopy of whole-mount negatively stained bacterial preparations. Biochemical analysis indicated that the protein monomers were post-translationally modified. 3D electron tomographic reconstruction and structure analyses of the functional domain revealed three well-defined subdomains (SI, SII and SIII) with a linker region between SII and SIII. Structural changes were observed in all three subdomains and the linker region of the adhesins synthesized compared with the known structure. These changes however did not affect the ability of the strain to bind collagen or form biofilms. The data suggest that changes in the composition of the glycan moiety alter the 3D structure of the molecule without negatively affecting the function(s) associated with this adhesin.

IMPORTANCE

The human oral pathogen A. actinomycetemcomitans is a causative agent of periodontal and several systemic diseases. EmaA is a trimeric autotransporter protein adhesin important for the colonization of this pathobiont in vivo. This adhesin is modified with sugars associated with the O-polysaccharide (O-PS) and the modification is mediated using the same enzymes involved in lipopolysaccharide (LPS) biosynthesis. The interaction with collagen is not mediated by the specific binding between the glycans and collagen but is attributed to changes in the final quaternary structure necessary to maintain an active adhesin. In this study, we have determined that the composition of the sugars utilized in the post-translational modification of this adhesin is exchangeable without compromising functional activities.
p115RhoGEF activates RhoA to support tight junction maintenance and remodeling
Authors: Chumki Shahana A. , van den Goor Lotte M. , Hall Benjamin N. , Miller Ann L.
Published: June 2022

In vertebrates, epithelial cell-cell junctions must rapidly remodel to maintain barrier function as cells undergo dynamic shape-change events. Consequently, localized leaks sometimes arise within the tight junction (TJ) barrier, which are repaired by short-lived activations of RhoA, called “Rho flares”. However, what activates RhoA at leak sites remains unknown. Here, we asked which guanine nucleotide exchange factor (GEF) localizes to TJs to initiate Rho activity at Rho flares. We find that p115RhoGEF locally activates Rho flares at sites of barrier leaks and TJ loss. Knockdown of p115RhoGEF leads to diminished Rho flare intensity and impaired TJ remodeling. p115RhoGEF knockdown also decreases junctional active RhoA levels, thus compromising the apical actomyosin array and junctional complex. Furthermore, p115RhoGEF is necessary to preserve global TJ barrier function by promoting local leak repair and preventing repeating leaks. In all, our work demonstrates a central role for p115RhoGEF in activating junctional RhoA to preserve barrier function and direct local TJ remodeling.
Phenotypic Heterogeneity in the DNA Replication Stress Response Revealed by Quantitative Protein Dynamics Measurements
Authors: Ho Brandon , Loll-Krippleber Raphael , Torres Nikko P. , Cuny Andreas , Rudolf Fabian , Brown Grant W.
Published: June 2022

Cells respond to environmental stressors by activating programs that result in protein abundance and localization changes. The DNA damage and DNA replication stress responses have been heavily studied and provide exemplars of the roles of protein localization and abundance regulation in proper cellular stress response. While vast amounts of data have been collected to describe the dynamics of yeast proteins in response to numerous external stresses, few have assessed and compared both protein localization kinetics and phenotypic heterogeneity in the same context, particularly during DNA replication stress. We developed a robust yet simple quantification scheme to identify and measure protein localization change events (re-localization) and applied it to the 314 yeast proteins whose subcellular distribution changes following DNA replication stress. We captured different kinetics of protein re-localization, identified proteins with localization changes that were not detected in previous analyses, and defined the extent of heterogeneity in stress-induced protein re-localization. Our imaging platforms and analysis pipeline enables efficient measurements of protein localization phenotypes for single cells over time and will guide future work in elucidating the biological parameters that govern cellular heterogeneity.
Discovery of a Gut Bacterial Metabolic Pathway that Drives α-Synuclein Aggregation and Neurodegeneration
Authors: Ortiz de Ora Lizett , Uyeda Kylie S. , Bess Elizabeth
Published: June 2022

Parkinson’s disease (PD) etiology is associated with aggregation and accumulation of α-synuclein (α- syn) proteins in midbrain dopaminergic neurons. Emerging evidence suggests that in certain subtypes of PD, α-syn aggregates originate in the gut and subsequently spread to the brain. However, the mechanisms that instigate α-syn aggregation in the gut have remained elusive. In the brain, the aggregation of α-syn is induced by oxidized dopamine. Such a mechanism has not been explored in the gastrointestinal (GI) tract, a niche harboring 46% of the body’s dopamine reservoirs. Here, we report that gut bacteria Enterobacteriaceae induce α-syn aggregation. More specifically, our in vitro data indicate that respiration of nitrate by Escherichia coli K-12 yields nitrite, a potent oxidizing agent that creates an oxidizing redox potential in the bacterial environment. In these conditions, Fe2+ was oxidized to Fe3+, enabling formation of dopamine-derived quinones and α-syn aggregates. Exposing nitrite, but not nitrate, to enteroendocrine STC-1 cells induced aggregation of α-syn that is natively expressed in these cells, which line the intestinal tract. Finally, we examined the in vivo relevance of bacterial nitrate respiration to the formation of α-syn aggregates using Caenorhabditis elegans models of PD. We discovered that nematodes exposed to nitrate-reducing E. coli K-12 displayed significantly enhanced neurodegeneration as compared to an E. coli K-12 mutant that could not respire nitrate. This neurodegenerative effect was absent when α-syn was mutated to prevent interactions with dopamine-derived quinones. Taken together, our findings indicate that gut bacterial nitrate reduction may be critical to initiating intestinal α- syn aggregation.

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