bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stomatal patterning is differently regulated in adaxial and abaxial epidermis in Arabidopsis
Authors: Jalakas Pirko , Tulva Ingmar , Bērziņa Nele Malvīne , Hõrak Hanna 
Published: August 2024

Abstract
Stomatal pores in leaves mediate CO2 uptake into the plant and water loss via transpiration. Most plants are hypostomatous with stomata present only in the lower leaf surface (abaxial epidermis). Many herbs, including the model plant Arabidopsis, have substantial numbers of stomata also on the upper (adaxial) leaf surface. Studies of stomatal development have mostly focused on abaxial stomata and very little is known of adaxial stomatal formation. We analysed the role of leaf number in determining stomatal density and stomatal ratio, and studied adaxial and abaxial stomatal patterns in Arabidopsis mutants deficient in known abaxial stomatal development regulators. We found that stomatal density in some genetic backgrounds varies between different fully expanded leaves, and thus we recommend using defined leaves for analyses of stomatal patterning. Our results indicate that stomatal development is at least partly independently regulated in adaxial and abaxial epidermis, as (i) plants deficient in ABA biosynthesis and perception have increased stomatal ratios, (ii) the epf1epf2, tmm, and sdd1 mutants have reduced stomatal ratios, (iii) erl2 mutants have increased adaxial but not abaxial stomatal index, and (iv) stomatal precursors preferentially occur in abaxial epidermis. Further studies of adaxial stomata can reveal new insights into stomatal form and function.
Extra cut-off value of aldosterone-to-renin ratio for screening primary aldosteronism in hypertensive patients with diabetes mellitus
Authors: Chen Dubo , Li Yuzhe , Wu Jiayin , Lin Wenbin , Zhong Liangying , Feng Pinning , Gan Wenjia 
Published: August 2024

Abstract
Primary aldosteronism (PA) and diabetes mellitus (DM) may coexist. We previously found that DM and impaired glucose tolerance (IGT) may decrease the efficiency of the aldosterone-to-renin ratio (ARR) for screening PA. Thus, we wanted to determine appropriate ARR cut-off values for screening PA in patients with hypertension with DM and IGT. Data from 736 patients with hypertension were collected. They were divided into PA (77 cases), PA with DM (27 cases), PA with IGT (44 cases), hypertension without PA (353 cases), hypertension with DM (without PA, 127 cases), and hypertension with IGT (without PA, 108 cases). Receiver operating characteristic (ROC) curves were used to identify the appropriate ARR cut-off values in different conditions. Screening efficiencies of these cut-off values were evaluated across different groups. ARR cut-off values for screening PA in hypertensive patients without DM and IGT, with DM, and with IGT were 29.65, 23.15, and 26.9, respectively. All cut-off values demonstrated high sensitivity and specificity: 92.2% and 88.7%, 92.6% and 79.5%, and 88.6% and 85.2%, respectively, and areas under the ROC curves were 0.941, 0.904, and 0.909, respectively. Our results suggest that extra ARR cut-off values may be necessary for effective screening PA in hypertensive patients with DM and IGT, particularly in those with DM.
Placental site nodules and reproductive outcomes: a clinicopathologic case series
Authors: Jain Meaghan , Peterson Andrea , Sapna Fnu , Hebert Tiffany , Lieman Harry 
Published: August 2024

Abstract

Background
Placental site nodules (PSNs) are benign tumor-like growths that develop from chorionic-type intermediate trophoblastic cells. Their clinical significance is unknown. This study aims to determine the risk factors associated with PSNs, with focus on possible reproductive impact.

Methods
We performed a retrospective case series of all patients with a pathology diagnosis of PSN in a large urban hospital system from 2018 to 2022. We collected clinical variables such as pathology diagnosis/description, presenting symptoms, method of prior delivery, and prior history of infertility, pregnancy loss, and uterine instrumentation.

Results
A total of 32 patients were included in this case series. The most common presenting symptom was abnormal uterine bleeding (40.6%, 13/32). Recurrent pregnancy loss (RPL) (15.6%, 5/32) and infertility (15.6%, 5/32) were common presenting symptoms as well. 62.5% (20/32) patients had a history of prior uterine instrumentation. Coexisting chronic endometritis was identified in 9.4% (3/32) of cases. Of the 5 RPL/infertility patients who underwent hysteroscopic resection of a PSN, 1 achieved a live birth.

Conclusion
PSNs may be associated with abnormal uterine bleeding, recurrent pregnancy loss, infertility, history of prior uterine instrumentation, and chronic endometritis. Although a rare diagnosis, the presence of a PSN should be considered in patients presenting for infertility or recurrent pregnancy loss workup.
The Nature of Non-discrimination Obligations Contained in International Investment Treaties
Authors: Risvas Michail 
Published: August 2024

Abstract
This chapter focuses on the nature of non-discrimination obligations within international investment treaties. It outlines the paradigms of discrimination in the US, EU, and human rights anti-discrimination law: disparate treatment and disparate impact discrimination. In domestic and international courts, circumstantial evidence and adverse inferences play a vital role in proving disparate treatment or direct discrimination amidst cases. The chapter explains that all non-discrimination obligations contained in investment treaties fall within the disparate treatment discrimination paradigm and explains the implications. It then explores the relationship between the different non-discrimination obligations in international investment treaty arbitration, which includes the key concepts of fair and equitable treatment (FET), discrimination, expropriation, National Treatment and most favoured nations (MFN).
Psychological Risk Factors for Delayed Recovery Among Active Duty Service Members Seeking Treatment for Musculoskeletal Complaints at a Navy Shore-Based Military Medical Treatment Facility
Authors: Mowery Hope C , Campello Marco , Ziemke Gregg , Oh Cheongeun , Hope Timothy , Jansen Brittany , Weiser Sherri 
Published: August 2024

ABSTRACT

Introduction
Musculoskeletal injuries (MSIs) are a leading cause of separation from the U.S. Navy. Data have shown that several psychological responses to MSI are associated with treatment outcomes. Yellow flags are maladaptive psychological responses to injury and predict delayed recovery, whereas pink flags indicate resilience after MSI and are associated with good treatment outcomes. Identifying these factors in patients with MSI would permit early targeted care to address factors that may delay their readiness for deployment and enhance factors that support recovery.

Materials and Methods
Active duty service members with MSI who reported to physical therapy outpatient services at a naval hospital were recruited for the study. Yellow flags were assessed at baseline as part of a larger study. Participants completed the Fear Avoidance Beliefs Questionnaire (with two subscales, physical activity and work), the Pain Catastrophizing Scale, and the Hospital Anxiety and Depression Scale. Clinically relevant cut-off scores were used to indicate risk factors of delayed recovery. Pink flags were assessed with the Pain Self-Efficacy Questionnaire and a measure of positive outcome expectations for recovery.

Results
Two hundred and ninety participants responded to some or all of the questionnaires. Of these, 82% exceeded the cut-off scores on the physical activity subscale of the Fear Avoidance Beliefs Questionnaire, and 39% did so on the work subscale. Pain catastrophizing exceeded the cut-off in only 4.9% of the sample. Forty-three percent of these exceeded the cut-off for the anxiety subscale of the Hospital Anxiety and Depression Scale; 27% exceeded the cut-off on the depression subscale of the Hospital Anxiety and Depression Scale. Additionally, 54% endorsed scores greater than 40 on the Pain Self-Efficacy Questionnaire, and 53% endorsed a high score on the positive outcome expectations.

Conclusions
A substantial portion of the sample endorsed elevated scores on one or more indicators of delayed recovery from MSI. Most participants showed a fear of physical activity, and approximately half reported pain-related distress (anxiety and depression). In addition, feelings of self-efficacy and positive outcome expectations of treatment were endorsed by only about half of the participants, indicating that the remaining half did not report adaptive responses to MSI. Early identification of these risk factors will allow for targeted treatment approaches that incorporate these yellow flags into treatment and support a psychologically informed approach to physical therapy. This approach is likely to reduce delayed recovery and improve deployment readiness.
Assessing Survival, Distribution, and Optimal Loading Technique of Schwann Cell–Derived Exosomes Into Second-generation Axon Guidance Channels
Authors: Errante Emily L , Smartz Taylor , Costello Meredith C , Schaeffer Ericka A , Kloehn Andrew J , Yunga Tigre Joseph , Khan Aisha , Pressman Yelena , Levi Allan D , Burks S Shelby 
Published: August 2024

ABSTRACT

Introduction
Peripheral nerve injury (PNI) occurs in approximately 3% of all trauma patients and can be challenging to treat, particularly when injury is severe such as with a long-segmental gap. Although peripheral nerves can regenerate after injury, functional recovery is often insufficient, leading to deficits in the quality of life of patients with PNI. Although nerve autografts are the gold standard of care, there are several disadvantages to their use, namely a lack of autologous nerve material for repair. This has led to the pursuit of alternative treatment methods such as axon guidance channels (AGCs). Second-generation AGCs have been shown to be able to deliver growth-enhancing substrates for nerve repair directly to the injury site. Although our laboratory has had success with second-generation AGCs filled with Schwann cells (SCs), SCs have their own set of issues clinically. Because of this, we have begun to utilize SC-derived exosomes as an alternative, as they have the appropriate protein markers, associate to axons in high concentrations, and are able to improve nerve regeneration. However, it is unknown how SC-derived exosomes may react within second-generation AGCs; thus, the aim of the present study was to assess the ability of SC-derived exosomes to be loaded into a second-generation AGC and how they would distribute within it.

Materials and Methods
A total of 4 dry second-generation AGCs were loaded with SC-derived exosomes that were derived from green fluorescent protein (GFP)-labeled SCs. They were subsequently frozen and sliced before imaging.

Results
Here, we present findings that SC-derived exosomes can be loaded into second-generation AGCs through our established loading method utilizing negative pressure and are able to survive and equally distribute along the length of the AGC.

Conclusions
Although only 4 second-generation AGCs were utilized, these findings indicate a potential use for SC-derived exosomes within second-generation AGCs to treat severe PNI. Future research should focus on exploring this in greater detail and in different contexts to assess the ability of SC-derived exosomes to survive at the site of injury and treat PNI.
Outpatient Prescriptions for Insomnia Medications During the First Year Following Combat-Related Amputations
Authors: Melcer Ted , Zouris James , MacGregor Andrew , Crouch Daniel , Sheu Robert , Galarneau Michael 
Published: August 2024

ABSTRACT

Introduction
Sleep-related disorders are associated with pain, fatigue, and deficits in cognitive performance, which may interfere with successful rehabilitation. The study objectives were to (1) quantify outpatient prescriptions for insomnia medications during the first year following combat-related amputations, (2) examine longitudinal changes in prescriptions for insomnia medications, and (3) analyze patient characteristics associated with prescriptions for insomnia medications.

Material and Methods
This was a retrospective study of DoD casualty records from the Expeditionary Medical Encounter Dataset and prescriptions for outpatient medications from the Pharmacy Data Transaction Service. Patients were a total of 1,651 U.S. service members who sustained major limb amputations in Operations Iraqi and Enduring Freedom from 2001 through 2017 and had outpatient prescriptions for any medication during the first year postinjury. Prescriptions for medications recommended for insomnia were low-dose antidepressants, anxiolytic sedatives, benzodiazepines, melatonin receptor agonist, and low-dose quetiapine. These prescription medications were analyzed by medication type, postinjury time, and patient characteristics during the first year postinjury.

Results
During the first year postinjury, 78% of patients (1,291 of 1,651) had outpatient prescriptions for insomnia medications, primarily anxiolytic sedative drugs (e.g., zolpidem), averaging a total of 86 prescription days (median = 66). The prevalence of these prescriptions declined substantially during the first year, from 57% of patients during the first quarter to 28% during the fourth quarter postinjury. In univariate analyses, multiple patient characteristics, including high Injury Severity Score, continued opioid and non-opioid analgesic prescriptions, and diagnoses of chronic pain, mood disorder, and posttraumatic stress disorder, were significantly associated with higher prevalence and duration of outpatient prescriptions for insomnia medications.

Conclusions
The present results indicate a high prevalence of outpatient prescriptions for insomnia medications following combat-related amputations, a prevalence that is substantially higher than previously reported among active duty personnel. These findings can inform DVA/DoD guidelines for amputation care and insomnia among military subpopulations. The results highlight the need for more research on the treatment of insomnia during early postinjury rehabilitation among patients who sustained serious combat injuries.
Sudden Hearing Loss in the Active Duty Population: An Epidemiological Study
Authors: Sommerfeldt John M , Jermihov Anastasia P , Erbele Isaac D , Chen Brian S 
Published: August 2024

ABSTRACT

Introduction
Hearing loss among military personnel is a well-known challenge, reported as the second most common VA service-connected disability. Although most hearing loss occurs gradually, a subset occurs suddenly and significantly impacts quality of life and military readiness and is considered as a medical emergency. This study aims to evaluate the incidence of sudden hearing loss among different subpopulations within the military system to better identify at-risk groups.

Materials and Methods
This study was a retrospective population-based study reviewing all cases of diagnosed sudden hearing loss between January 1, 2016 and December 31, 2021 within active duty service members in the U.S. DoD. Statistical analysis of multiple subpopulations was performed.

Results
There were 2,650 cases of sudden hearing loss diagnosed in active duty service members during the study period, with an average incidence of 32.9 cases per 100,000 people per year, compared with 5 to 27 cases per 100,000 people per year reported in civilian populations. Senior officers demonstrated significantly increased rates of sudden hearing loss with 103.9 cases per 100,000 people per year, likely as a result of increased age, as did Air Force personnel with 45.1 cases per 100,000 people per year. There was no difference in incidence based on military occupational specialty, though service members located overseas were noted to have decreased incidence compared with those stationed within the USA. There was no significant difference during the years before coronavirus-19 pandemic (2016-2019) compared to the years following the start of the pandemic (2020-2021).

Conclusions
Sudden hearing loss appears to occur more frequently in military personnel than in the civilian population. The increased incidence in senior officers is likely driven by increased age, though further evaluation into the discrepancies between reported incidence of hearing loss among enlisted service members and officers is warranted. Although military occupational specialty did not demonstrate any significant difference in incidence, for thus far unknown reasons those in the Air Force demonstrated increased rates of sudden hearing loss. Although other potentially at-risk groups were identified, focused efforts to better understand contributing factors to elevated incidence in senior officers and Air Force personnel will help to better mitigate the incidence and effects of sudden hearing loss.
Prolongation of the Time Window From Traumatic Limb Amputation to Replantation From 6 to 33 Hours Using Ex Vivo Limb Perfusion
Authors: Zhang Lei , Ipaktchi Ramin , Ben Brahim Bilal , Arenas Hoyos Isabel , Jenni Hansjörg , Dietrich Lena , Despont Alain , Shaw-Boden Jane , Büttiker Svenja , Siegrist David , Gultom Mitra , Parodi Chiara , Garcia Casalta Luisana , Petrucci Mariafrancesca , Petruccione Ilaria , Mirra Alessandro , Nettelbeck Kay , Wang Junhua , de Brot Simone , Voegelin Esther , Casoni Daniela , Rieben Robert 
Published: August 2024

ABSTRACT

Introduction
Continuous extracorporeal perfusion (ECP), or machine perfusion, holds promise for prolonged skeletal muscle preservation in limb ischemia-reperfusion injury. This study aimed to extend the amputation-to-replantation time window from currently 6 hours to 33 hours using a 24-hour ECP approach.

Materials and Methods
Six large white pigs underwent surgical forelimb amputation under general anesthesia. After amputation, limbs were kept for 9 hours at room temperature and then perfused by 24-hour ECP with a modified histidine-tryptophan-ketoglutarate (HTK) solution. After ECP, limbs were orthotopically replanted and perfused in vivo for 12 hours. Clinical data, blood, and tissue samples were collected and analyzed.

Results
All 6 forelimbs could be successfully replanted and in vivo reperfused for 12 hours after 9 hours of room temperature ischemia followed by 24 hours ECP. Adequate limb perfusion was observed after replantation as shown by thermography and laser Doppler imaging. All pigs survived without severe organ failure, and no significant increase in inflammatory cytokines was found. Macroscopy and histology showed marked interstitial muscular edema of the limbs, whereas myofiber necrosis was not evident, implying the preservation of muscular integrity.

Conclusions
The use of a 24-hour ECP has successfully extended limb preservation to 33 hours. The modified histidine-tryptophan-ketoglutarate perfusate demonstrated its ability for muscle protection. This innovative approach not only facilitates limb replantation after combat injuries, surmounting geographical barriers, but also broadens the prospects for well-matched limb allotransplants across countries and continents.
Impact of En Route Critical Care Provider Experience on Lung Protective Ventilation Compliance During Air Transport of Combat Wounded
Authors: Davis William T , Strilka Richard , Valdez-Delgado Krystal K , Burkhardt Josh , Medellin Kimberly L , Arana Allyson A , Savell Shelia C , Maddry Joseph K 
Published: August 2024

ABSTRACT

Introduction
The primary objective of this study was to evaluate the association between the U.S. Air Force Critical Care Air Transport (CCAT) provider operational experience with compliance for lung protective ventilation (LPV) volumes recommended by Acute Respiratory Distress Syndrome Clinical Network guidelines.

Materials and Methods
We performed a retrospective cohort study of CCAT providers transporting combat casualties requiring mechanical ventilation from the Middle East to Germany from 2007 to 2012. We reviewed CCAT medical records from 2007 to 2012 for the total number of patient transports by CCAT physicians and respiratory care practitioners (RCPs). Center for Sustainment of Trauma and Readiness Skills Cincinnati process improvement questionnaire data described provider demographics and clinical backgrounds. We linked these data to patient demographics and in-flight ventilation management from a prior CCAT cohort study. Patient inclusion criteria included transport by CCAT from the Middle East to Germany for traumatic injury requiring mechanical ventilation between 2007 and 2012. We excluded patients with no documented height or tidal volume. LPV compliance was defined as tidal volumes ≤8 mL/kg of predicted body weight during en route critical care transport. We performed a logistic regression analysis. This study was reviewed and approved by the 59th Medical Wing institutional review board (IRB).

Results
We analyzed 491 patient transports conducted by 71 (RCPs and 84 physicians. Patients had a median age of 25 years (IQR 22-30), 98% were male, median injury severity score was 24 (IQR 17-34), and median preflight PaO2/FiO2 was 285 (IQR 220-365). Median experience was 26 missions (IQR 13-40) for RCPs and 23 missions (IQR 12-38) for physicians. All in-flight tidal volumes were LPV compliant in 58.3% of missions. Unadjusted analysis showed higher LPV compliance for RCPs with in-garrison critical care experience. Multivariate models did not find an association between missions flown and LPV compliance but did demonstrate a positive association with physician specialty of medical intensivist (OR 3.0, 95% CI 1.6-5.7) and a negative association with flights in 2008 (OR 0.4, 95% CI 0.2-0.7) for LPV compliance.

Conclusion
No association was found between number of missions flown by CCAT providers and lung protective tidal volume compliance. Linkage of multiple data sources enabled investigation of clinical and operational currency associations with a care quality metric compliance in the combat en route care environment. Future studies should evaluate the impact of ongoing CCAT training and quality improvement interventions on LPV compliance.