bluuebunny/crossref_metadata_2025 huggingface dataset:
Henoch–Schönlein purpura with antecedent allergic diseases in a 4-year-old child: a case report
Authors: Bista Satkirti , Adhikari Yuvraj , Karmacharya Sammridhi , Joshi Sagar , Pandey Shikha , Adhikari Nawaraj
Published: May 2023

Introduction and importance:

Henoch–Schönlein purpura (HSP)/immunoglobulin A vasculitis is an acute immunoglobulin-mediated vascular disorder compromising a triad of non-blanchable purpuric rashes, colicky abdominal pain and haematuria. Incidence ranging for large populations has been most common vasculitis among children with a mean age of 6years. Disease presentation ranges from small petechial rash to the most severe form of renal involvement so early diagnosis is important.

Case presentation:

Here the authors present a 4-year-old girl with antecedent allergic history associated HSP. She presented with non-blanchable purpuric rashes, abdominal pain with bilateral ankle swelling. She had been treated for atopic dermatitis and acute urticaria without angioedema and acute tonsillitis. The potential association of HSP and these condition should be kept in mind in order not to miss the impediment complications of HSP.

Clinical discussion:

HSP usually presents with rash, abdominal pain and vomiting, joint pain especially involving knees and ankles, subcutaneous oedema but in severe cases there could be renal involvement leading to nephritis, neurological manifestation involving neuropathies, altered mental status and many others.

Conclusion:

This case highlights the rarity of disease, presentation, association with allergic diseases and availability of treatment modality.
Sarcopenia and associated risk factors in oncology outpatients in specialized cancer centers in Saudi Arabia: a cross-sectional study
Authors: Almouaalamy Nabil , Adem Sittelbenat H. , Alsubhi Abdulrahman A. , Alansari Ahmed B. , Yahya Marwan A. , Alsadan Sultan A.
Published: May 2023

Background:

Sarcopenia is a comorbidity associated with cancer, which takes advantage of a patient’s deteriorating state and decreases the survival rate. Thus, early detection of sarcopenia could improve oncology outpatient prognosis, treatment, and general quality of life.

Objective:

To measure the prevalence of probable sarcopenia and the associated risk factors in patients with cancer.

Methods:

This is a cross-sectional study. A total of 324 cancer patients were screened for sarcopenia using a simple questionnaire to rapidly diagnose sarcopenia [SARC-F (strength, assistance with walking, rising from a chair, climbing stairs, and falls)] and a hand grip dynamometer tool. The study was conducted from 1 January 2021 till 28 February 2021, in the outpatient department of Princess Noorah Oncology Center.

Results:

Among 324 cancer patients receiving active chemotherapy treatment, 28.4% screened positive for sarcopenia (SARC-F score ≥4). Moreover, 23.45% were identified as probable cases [SARC-F score ≥4 and a low hand grip strength (HGS)] of sarcopenia, according to the European Working Group on Sarcopenia in Older People consensus 2 (EWGSOP2) case-finding algorithm, which is sufficient to initiate a management plan.

Conclusions:

One-quarter of the cancer patients had probable sarcopenia at our institution. Sarcopenia risk was independently associated with patient age, and the risk of sarcopenia was low among patients with higher albumin concentrations. Screening cancer patients for sarcopenia using the SARC-F questionnaire and HGS may offer a useful strategy to mitigate the risk of unfavorable consequences that may occur during cancer treatment.
Kartagener’s syndrome with recurrent respiratory infection: a case report
Authors: Poudel Sabin , Basnet Anuj , Bista Satkirti , Shah Ravi , Chhetri Binita Thapa
Published: May 2023

Introduction and importance:

Kartagener’s syndrome is a rare, ciliopathic autosomal recessive genetic disorder that comprises a triad of situs inversus, chronic sinusitis, and bronchiectasis leading to recurrent respiratory infections due to ciliary dyskinesia and thereby progressive deterioration of lung function. Additional clinical features of infertility, otitis media, and rhinitis are also seen in patients.

Case presentation:

The authors hereby present a case of Kartagener’s syndrome in a 40-year-old male with a repeated respiratory infection and bronchial asthma. He was received at the emergency room with symptoms of hemoptysis, shortness of breath, and chest pain. Diagnosis of cystic bronchiectasis with superadded infection was made based on clinical examinations and radiological assessments. He was treated in high-dependency unit. After 5 days of relieving therapeutic interventions in the hospital, he was discharged without further complication.

Clinical discussions:

Early diagnosis of Kartagener’s syndrome is likely to be beneficial as it helps delay deterioration of lung function to prevent complications and improve the quality of life of patients but the diagnosis of this syndrome is usually delayed as it is a rare disease, especially in countries with lack of complex diagnostic facilities. So, assessment for this syndrome has to be done in patients presenting with chronic and recurrent respiratory infections for correct timely diagnosis to have a good patient-centric healthcare facility.
Management of mad honey intoxication with suspected anaphylaxis in Nepal: a case report
Authors: Anand Ayush , Adhikari Nabin , Gupta Ashwini , Ranjan Rajesh , Gautam Arun , Bhattarai Urza , Shah Bhupendra
Published: May 2023

Introduction:

Consumption of mad honey can lead to intoxication. The exact incidence of mad honey-induced intoxication is unknown. Typically, the patients present with dizziness, nausea, syncope, and sinus bradycardia.

Case presentation:

The authors reported the case of a middle-aged male patient who presented with blurring of vision, passage of loose stools, vomiting, and profuse sweating after ingestion of honey. He also had a history of loss of consciousness. On presentation, he was hypotensive and tachypneic with cold, clammy extremities. His ECG showed sinus bradycardia. The authors made a diagnosis of mad honey intoxication with suspected anaphylaxis. The authors treated him with intravenous normal saline, epinephrine, and atropine. He again developed hypotension and bradycardia in a few hours, for which hydrocortisone was administered, following which his heart rate was normalized in 2 h. Overall, the recovery time in our patient was 8 h. The patient was counseled to avoid consuming mad honey and did well on his monthly follow-up.

Discussion:

Our patient had signs and symptoms suggesting intoxication following ingestion of mad honey with suspicion of anaphylaxis. Similar to other reported cases, the patient had sinus bradycardia and hypotension. Epinephrine and atropine were administered to treat hypotension and bradycardia, respectively. Also, refractory hypotension was managed by intravenous hydrocortisone. Usually, atropine and saline infusion are sufficient to manage these cases, and simultaneous use of epinephrine and atropine should be avoided unless indicated.

Conclusion:

Our case highlighted the approach to diagnosing and treating mad honey intoxication with suspected anaphylaxis.
Survival status and predictors of mortality among COVID-19 patients admitted to intensive care units at COVID-19 centers in Addis Ababa, Ethiopia: a retrospective study
Authors: Boka Abdissa , Tadesse Addisu , W/Yohannes Getachew , Hussein Kedir
Published: May 2023

Introduction:

Worldwide, including in Ethiopia, there is an increased risk of coronavirus disease 2019 (COVID-19) disease severity and mortality. This study aimed to assess the survival status and predictors of mortality among COVID-19 patients admitted to the intensive care unit.

Methods:

This study included 508 COVID-19 patients retrospectively who were under follow-up. The work has been reported in line with the STROCSS (strengthening the reporting of cohort, cross-sectional and case–control studies in surgery) criteria. The data were collected through a systematic sampling from patients’ charts. Kaplan–Meier survival curves and logrank test, and Cox’s regression analyses were conducted to check the difference among categories of covariates and to identify predictors of mortality, respectively.

Results:

All patient charts were reviewed and the information was recorded. The average age (mean+SD) of these patients was 62.1+13.6 years. Among study participants, 422 deaths occurred and the mortality rate was 64.1 per 1000 person-days. The median survival time was 13 days [interquartile range (IQR): 10–18]. The significant predictors for this survival were: Age>45 years [adjusted hazard ratio (AHR)=4.34, 95% CI: 2.46–7.86], Diabetes mellitus (AHR=1.37, 95% CI: 1.05–1.77), Hypertension (AHR=1.39, 95% CI: 1.09–1.79), Renal disease (AHR=1.86, 95% CI: 1.01–3.43), Hypotension (AHR=1.71, 95% CI: 1.28–2.27), Electrolyte treatment (AHR=0.78, 95% CI: 0.63–0.97).

Conclusion:

The median survival of COVID-19 patients after their admission was 13 days, and predictors for this time were advanced age, preexisting comorbidities (like diabetes mellitus, hypertension, and renal disease), hypotension, and electrolyte therapy.
Factors associated with a higher need for antihypertensive medications at 12-months in postkidney transplant recipients: a retrospective cohort study
Authors: Arabi Ziad , Bawazir Abdullah S. , Arabi Tarek , Fawzy Nader A. , Baduwaylan Reem A. , Sabbah Belal
Published: May 2023

Background:

There are limited data on why some kidney transplant (KTx) recipients (KTRs) have ‘difficult-to-control (DTC) hypertension’ requiring greater than or equal to 2 antihypertensive medications while others require less antihypertensive medications post-KTx.

Methods:

The authors reviewed the pre-KTx cardiovascular (CV) imaging, and the changes of CV risk factors during the first-year post-KTx. The authors divided patients according to the number of their blood pressure medications at one year into two groups: requiring less than or equal to 1 and requiring greater than or equal to 2 medications (DTC hypertension). The target blood pressure during the time of this study was less than 140/90 mmHg.

Results:

Two hundred forty-five KTRs were included with an average age of 43.2. 56.3% were male and 79.2% were living donor KTRs. Pre-emptive KTx was 6.5%, previous coronary artery disease was 12.7%, diabetes and smoking 40.8 and 9%, respectively. 38% of the patients had DTC HTN. Risk factors were age (P<0.01), pre-KTx hypertension (P<0.01), and diabetes mellitus (P<0.01). Dialysis vintage, type of dialysis, type of KTx, and smoking were not different between the groups.

Patients with abnormal pre-KTx CV imaging, including abnormal ejection fraction less than 55% (P=0.03), abnormal wall motion on echocardiography (P<0.01), abnormal perfusion stress test (P<0.01), higher calcium scoring (P<0.01), abnormal cardiac catheterization (P<0.01), or higher degree of calcifications on CT of pelvic arteries (P<0.01) were at higher risk of DTC hypertension. Post-KTx factors including rejection, change in serum creatinine and weight, A1c, new-onset diabetes post-KTx, and persistent hyperparathyroidism were not different between the groups.

Multivariate analysis revealed associations with age (aOR=1.027), male sex (aOR=2.057), baseline diabetes mellitus (aOR=2.065), baseline HTN (aOR=2.82), and use of greater than or equal to 2 antihypertensive medications at 1-month post-KTx (aOR=6.146).

Conclusion:

At one year post transplantation, about a third of the KTRs required had DTC HTN. These patients were more likely to be older, males, diabetics, previously hypertensive, on greater than or equal to 2 HTN medications at 1-month post-KTx, and to have abnormal baseline pretransplant CV imaging.
Pulmonary artery aneurysm and hemoptysis as uncommon sequelae of COVID-19 infection: a case report from Syria
Authors: Hamdar Hussein , Nahle Ali Alakbar , Sikaria Amjad , Alhadid Salem Algomaa
Published: May 2023

Introduction and importance:

Pulmonary artery aneurysm (PAA) is a rare vascular disease, and it is known to be an extremely rare complication following infection with the coronavirus disease 2019 (COVID-19). Other etiologies of the disease are cancer, congenital heart anomalies, and vasculitis. While it is usually an asymptomatic disease, PAA can sometimes present with severe symptoms such as hemoptysis due to the rupture of the aneurysm.

Case presentation:

Here, The authors report a case of a 75-year-old female patient presented with hemoptysis. She had normal vasculature on a previous computed tomography scan when she was diagnosed with COVID-19. Four months after having COVID-19, and with a computed tomographic pulmonary angiography -assisted diagnosis, the patient was later diagnosed with PAA.

Clinical discussion:

PAAs have a wide nonspecific range of symptoms. The main diagnostic test is computed tomography angiography. Treatment is still controversial with no definite agreement on the management.

Conclusion:

COVID-19 infections can cause severe damage to blood vessels, especially in the context of other etiologies that can further damage the vasculature. This report demonstrates the importance of patient follow-up and monitoring post-COVID-19 infection in reducing further complications and mortality.
Recent outbreak of diphtheria in Pakistan; short communication
Authors: Aaqil Syeda Ilsa , Ochani Sidhant , Hasibuzzaman Md. Al
Published: May 2023

Diphtheria, a vaccine-preventable bacterial infection caused by Corynebacterium diphtheria usually starts with sore throat and fever and often results in breathing difficulties, heart rhythm problems, and rarely membranous pharyngitis. Although nursing these complications can help most people survive diphtheria, but it can be deadly in 5–10% of cases with higher death rates observed in children under 5 years of age or adults above 40. For the year 2022, 92 cases have been reported by seven European countries. Sixty-six of the reported cases presented with cutaneous diphtheria caused by Corynebacterium diphtheria while cases of respiratory diphtheria have also been reported, including one fatal case. The increase in diphtheria cases can be linked to an increased volume of migrants from diphtheria-endemic countries causing transmission of pathogens from countries of origin to recipient countries. Today the authors can treat diphtheria infections by using antibiotics and also prevent the disease with a vaccine. General population should be given awareness and educated in regard to disease prevention and appropriately implement administration of Diphtheria and Tetanus Toxoids and Pertussis Vaccines among people at risk for their own protection and urgently call for an action to eliminate the disease before its further spread as an outbreak.
Linezolid-induced black hairy tongue in a patient treated for idiopathic granulomatous mastitis: a case report
Authors: Sethi Yashendra , Padda Inderbir , Fulton Matthew , Kaiwan Oroshay , Chopra Hitesh , Bin Emran Talha
Published: May 2023

Introduction and importance:

Linezolid-induced black hairy tongue (BHT) is a highly scarce adverse event of linezolid therapy. To date, there are very few reported cases in contemporary literature. The onset and mechanism of BHT are also not well understood.

Case report:

In this article, the authors report a case of BHT in a 28-year-old female following 5 days of therapy with linezolid. The patient recovered well within few days of discontinuation of the drug and maintaining oral hygeine. Patient reassurance and counselling was integral to the management.

Discussion and conclusion:

This case report and review depict a rare adverse effect of linezolid and discuss its clinical implications aiding healthcare professionals in an early diagnosis and cromulent management strategy. The authors also present a compilation of previously reported literature on linezolid-induced BHT to support the discussion.
Guillan-barre syndrome during COVID-19 pandemic: a case series from Syria
Authors: Labbad Ibrahim , Shammas Ibrahim , Abbas Aram , Alorfhli Ibrahim , Agha Mohamad S.
Published: May 2023

Background:

The Coronavirus was first discovered in December 2019 and quickly it turned into a pandemic called coronavirus disease 2019 (COVID-19). The main symptoms of infection with this virus were constitutional and respiratory symptoms. However, one-third of COVID-19 patients also developed neurologic manifestations, including Guillan-Barre syndrome (GBS), which was one of the most critical complications.

Case presentation:

In this paper, the authors present seven patients who suffered from GBS after being infected with the Coronavirus or in conjunction with the infection. Nerve conduction studies showed axonal type in four patients, and demyelinating type in three patients. Neurological symptoms were the initial symptoms in two patients and the presence of COVID-19 was later discovered. Most of the patients had an excellent recovery.

Conclusion:

In the medical literature, many articles have mentioned the association of GBS with the Coronavirus, and it is considered the most common peripheral neurologic complication for the virus, but this article is considered one of the very few articles that were published from the Middle East, especially from Syria. Guillain-Barre’s occurrence after infections is known, and the Coronavirus is one of the most important viruses of the era, which incited an increase in the number of Guillain-Barre patients.
Surgical Outcome and Treatment Trends in 1289 Infants with Micrognathia: A Multicenter Cohort
Authors: Resnick Cory M. , Rottgers S. Alex , Wright Joshua M. , Vyas Raj M. , Goldstein Jeffrey A. , Swanson Jordan W. , Padula Michael A. , Coghill Carl H. , Ahmad Irfan , Molter David W. , Menezes Maithilee D. , Naing Khatija W. , Cielo Christopher M. ,   On behalf of the Children’s Hospitals Neonatal Consortium Micrognathia Focus Group
Published: May 2023

Background:

Studies of infants with micrognathia, especially Robin sequence, are limited by its rarity and both phenotypic and diagnostic variability. Most knowledge of this condition is sourced from small, single-institution samples.

Methods:

This is a cross-sectional study including infants with micrognathia admitted to 38 Children’s Hospital Neonatal Consortium centers from 2010 through 2020. Predictor variables included demographic data, birth characteristics, cleft, and syndrome status. Outcome variables included length of stay, death, feeding or respiratory support, and secondary airway operations.

Results:

A total of 1289 infants with micrognathia had surgery to correct upper airway obstruction. Mean age and weight at operation were 34.8 ± 1.8 weeks and 3515.4 ± 42 g, respectively. A syndromic diagnosis was made in 150 (11.6%) patients, with Stickler (5.4%) and Treacher Collins (2.2%) syndromes being the most common. Operations included mandibular distraction osteogenesis (MDO) in 66.3%, tracheostomy in 25.4%, and tongue–lip adhesion (TLA) in 8.3%. Patients receiving a tracheostomy had lower birthweight, head circumference, gestational age, and Apgar scores. Patients undergoing MDO were less likely to need a second airway operation compared with patients undergoing TLA (3.5% versus 17.8%; P < 0.001). The proportion of infants feeding exclusively orally at hospital discharge differed significantly, from most to least: MDO, TLA, and tracheostomy. Hospital length of stay was not statistically different for patients who had MDO or TLA, but was longer for those with primary tracheostomy. The mortality rate was low for all operations (0.5%).

Conclusions:

In this surgical patient cohort, MDO was associated with shorter hospital stay, improved oral feeding, and lower rates of secondary airway operations. Prospective multicenter studies are necessary to support these conclusions.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Risk, III.
A Comprehensive Analysis of Risk Factors Associated With Inpatient Falls
Authors: Warren Carley , Rizo Eduardo , Decker Edward , Hasse Adam
Published: May 2023

Objectives

The primary objective of this study was to identify the relationship between rates of falls among hospitalized patients and the use of inpatient medications associated with falls.

Methods

This is a retrospective study on patients older than 60 years, hospitalized between January 1, 2021, and December 31, 2021. Ventilated patients and patients with a length of stay or fall less than 48 hours after admission were excluded. Falls were determined by assessing documented post fall assessments in the medical record. Patients who fell were matched 3:1 with control patients based on demographic data (age, sex, length of stay up to the fall time, and Elixhauser Comorbidity score). For controls, a pseudo time to fall was assigned based on matching. Medication information was gathered from barcode administration data. Statistical analysis was conducted using R and RStudio.

Results

A total of 6363 fall patients and 19,089 controls met the inclusion and exclusion criteria. Seven drug classes were identified as statistically significant (P < 0.001) in increasing an inpatient’s rate of falling: angiotensin-converting enzyme inhibitors (unadjusted odds ratio [OR], 1.22), antipsychotics (OR, 1.93), benzodiazepines (OR, 1.57), serotonin modulators (OR, 1.2), selective serotonin-reuptake inhibitors (OR, 1.26), tricyclics and norepinephrine reuptake inhibitors (OR, 1.45), and miscellaneous antidepressants (OR, 1.54).

Conclusions

Hospitalized patients older than 60 years are more likely to fall while taking angiotensin-converting enzyme inhibitors, antipsychotics, benzodiazepines, serotonin modulators, selective serotonin-reuptake inhibitors, tricyclics, norepinephrine reuptake inhibitors, or miscellaneous antidepressants. Patients on opiates and diuretics had a significant decrease in rate of falls.
Citation versus disruption in the military: Analysis of the top disruptive military trauma research publications
Authors: Dilday Joshua , Gallagher Shea , Bram Ryan , Williams Elliot , Grigorian Areg , Matsushima Kazuhide , Schellenberg Morgan , Inaba Kenji , Martin Matthew
Published: May 2023

BACKGROUND

Bibliometric analysis of surgical research has become increasingly prevalent. Citation count (CC) is a commonly used marker of research quality, but may overlook impactful military research. The disruption score (DS) evaluates manuscripts on a spectrum from most innovative with more positive scores (disruptive [DR]) to most entrenched with more negative scores (developmental; DV). We sought to analyze the most DR and DV versus most cited research in military trauma.

METHODS

Top trauma articles by DS and by CC were identified via professional literature search. All publications in military journals were included. Military trauma-related keywords were used to query additional top surgical journals for military-focused publications. Publications were linked to the iCite NIH tool for CC and related metrics. The top 100 DR and DV publications by DS were analyzed and compared with the top 100 articles by CC.

RESULTS

Overall, 32,040 articles published between 1954 and 2014 were identified. The average DS and CC were 0.01 and 22, respectively. Most articles were published in Mil Med (68%). The top 100 DR articles were frequently published in Mil Med (51%) with a mean DS of 0.148. Of these, the most cited article was only the 40th most disruptive. The top 100 CC articles averaged a DS of 0.009 and were commonly found in J Trauma (53%). Only five publications were on both the top 100 DR and top 100 CC lists; 19 were on both the top DV and CC lists. Citation count was not correlated with DR (r = −0.134; p = 0.07) and only weakly correlated with DV (r = 0.215; p = 0.003).

CONCLUSION

DS identifies publications that changed military paradigms and future research directions previously overlooked by citation count alone. The DR and DV articles are distinct with little overlap between highly cited military articles. Multiple bibliometric measures should be employed to avoid overlooking impactful military trauma research.

LEVEL OF EVIDENCE

Diagnostic Test or Criteria; Level IV.
The 16-year evolution of a military-civilian partnership: The University of Alabama at Birmingham experience
Authors: Rokayak Omar A. , Lammers Daniel T. , Baird Emily W. , Holcomb John B. , Jansen Jan O. , Cox Daniel B. , Winkler Jon P. , Betzold Richard D. , Manley Nathan R. , Northern David Marc , Wright James K. , Dorsch John , Kerby Jeffrey D.
Published: May 2023

BACKGROUND

At the University of Alabama at Birmingham (UAB), a multi-tiered military-civilian partnership (MCP) has evolved since 2006. We aimed to outline this model to facilitate potential replication nationally.

METHODS

We performed a comprehensive review of the partnership between UAB, the United States Air Force Special Operations Command, and the Department of Defense (DoD) reviewing key documents and conducting interviews with providers. As a purely descriptive study, this project did not involve any patient data acquisition or analysis and therefore was exempt from institutional review board approval per institutional policy.

RESULTS

At the time of this review, six core programs existed targeting training, clinical proficiency, and research. Training: (1) The Special Operations Center for Medical Integration and Development trains up to 144 combat medics yearly. (2) UAB trains one integrated military Surgery resident yearly with two additional civilian-sponsored military residents in Emergency Medicine. (3) UAB's Surgical Critical Care Fellowship had one National Guard member with two incoming Active-Duty, one Reservist and one prior service member in August 2022. Clinical Proficiency: (4) UAB hosts four permanently assigned United States Air Force Special Operations Command Special Operations Surgical Teams composed of general surgeons, anesthesiologists, certified registered nurse anesthetists, surgical technologists, emergency physicians, critical care registered nurses, and respiratory therapists totaling 24 permanently assigned active-duty health care professionals. (5) In addition, two fellowship-trained Air Force Trauma Critical Care Surgeons, one Active-Duty and one Reservist, are permanently assigned to UAB. These clinicians participate fully and independently in the routine care of patients alongside their civilian counterparts. Research: (6) UAB's Division of Trauma and Acute Care Surgery is currently conducting nine DoD-funded research projects totaling $6,482,790, and four research projects with military relevance funded by other agencies totaling $15,357,191.

CONCLUSION

The collaboration between UAB and various elements within the DoD illustrates a comprehensive approach to MCP. Replicating appropriate components of this model nationally may aid in the development of a truly integrated trauma system best prepared for the challenges of the future.

LEVEL OF EVIDENCE

Economic and Value-based Evaluations; Level IV.
Prolonging the zone 1 aortic occlusion time to 4 hours using a partial resuscitative endovascular balloon in a swine model
Authors: Ho Jessie W. , Jin Guang , Nguyen Jessica , Keeney-Bonthrone Toby P. , Diaz-Perez Dariel A. , Dawood Zaiba Shafik , Kemp Michael T. , Alam Jenna S. , Gauger Megan A. , Shaikh Aleezeh , Chtraklin Kiril , Liu Baoling , Alam Hasan B.
Published: May 2023

BACKGROUND

The clinical usage of the resuscitative endovascular balloon occlusion of the aorta (REBOA) is limited by distal ischemia resulting from complete aortic occlusion. We hypothesized that animals would physiologically tolerate the prolonged partial occlusion using the novel partially occluding REBOA (pREBOA) with survivable downstream injuries.

METHODS

This study used the pREBOA-PRO catheter in a previously established swine model. Female Yorkshire swine (n = 10) underwent a volume-controlled hemorrhage (40% estimated blood). After 1 hour of shock (mean arterial pressure, 28–32 mm Hg), animals were randomized to partial occlusion for either 2 hours or 4 hours. The pREBOA was inflated in zone 1 to achieve partial occlusion defined as a distal systolic blood pressure (SBP) of 20 ± 2 mm Hg. The balloon was deflated at the end of the occlusion period, and animals were resuscitated for 2 hours. Tissues were examined for gross and histologic injury. The primary endpoint was histologic organ injury, and secondary end points were hemodynamic variables and degree of distal organ ischemia.

RESULTS

All animals survived to the endpoint. Both groups had similar proximal and distal SBP at baseline, with a divergence of pressures ranging from 55 mm Hg to 90 mm Hg on inflation. The lactate levels increased throughout the occlusion and decreased approximately 40% during the observation period. More animals required norepinephrine and fluid in the 4-hour group compared with the 2-hour group. There was no gross small bowel ischemia noted in the 2-hour animals. The 4-hour group had surgically resectable patchy short segment ischemia. Neither group showed nonsurvivable organ ischemia on pathology or laboratory values.

CONCLUSION

This is the first study showing that the zone 1 aorta can be occluded for over 4 hours using a new pREBOA device without need for balloon titration. In conclusion, simple changes in balloon design offer reliable partial aortic occlusion, with potentially survivable and surgically manageable downstream injuries.
Auditory region circulation in Lagomorpha: the internal carotid artery pattern revisited
Authors: Ruf Irina , Meng Jin , Fostowicz-Frelik Łucja
Published: May 2023

The internal carotid artery (ICA) is one of the major vessels in the cranial circulation. Characters concerning the ICA, such as its course in the auditory region, have been employed frequently in phylogenetic analyses of mammals, including extinct taxa. In lagomorphs, however, our knowledge on vascular features of the auditory region has been based predominantly on living species, mostly on the European rabbit. We present the first survey on 11 out of 12 extant genera and key fossil taxa such as stem lagomorphs and early crown representatives (
Archaeolagus
and
Prolagus
). The ICA pattern shows a modified transpromontorial course in stem taxa (
Litolagus
,
Megalagus
and
Palaeolagus
) and
Archaeolagus
, which we propose as the ancestral character state for Lagomorpha, similar to that for the earliest rodents, plesiadapids and scandentians. The ICA pattern in leporids is perbullar, but shows structural similarities to stem taxa, whereas the extrabullar ICA course in
Ochotona
is apparently a highly derived condition.
Prolagus
shows a mixed character state between leporids and
Ochotona
in its ICA route. The persistence of the transpromontorial ICA course and similarities in the carotid canal structure among stem taxa and crown leporids support morphological conservatism in Lagomorpha, in contrast to their sister clade Rodentia.

This article is part of the theme issue ‘The mammalian skull: development, structure and function’.
A lung-specific mutational signature enables inference of viral and bacterial respiratory niche
Authors: Ruis Christopher , Peacock Thomas P. , Polo Luis M. , Masone Diego , Alvarez Maria Soledad , Hinrichs Angie S. , Turakhia Yatish , Cheng Ye , McBroome Jakob , Corbett-Detig Russell , Parkhill Julian , Floto R. Andres
Published: May 2023

Exposure to different mutagens leaves distinct mutational patterns that can allow inference of pathogen replication niches. We therefore investigated whether SARS-CoV-2 mutational spectra might show lineage-specific differences, dependent on the dominant site(s) of replication and onwards transmission, and could therefore rapidly infer virulence of emergent variants of concern (VOCs). Through mutational spectrum analysis, we found a significant reduction in G>T mutations in the Omicron variant, which replicates in the upper respiratory tract (URT), compared to other lineages, which replicate in both the URT and lower respiratory tract (LRT). Mutational analysis of other viruses and bacteria indicates a robust, generalizable association of high G>T mutations with replication within the LRT. Monitoring G>T mutation rates over time, we found early separation of Omicron from Beta, Gamma and Delta, while mutational patterns in Alpha varied consistent with changes in transmission source as social restrictions were lifted. Mutational spectra may be a powerful tool to infer niches of established and emergent pathogens.
Identifying therapeutic targets for cancer: 2,094 circulating proteins and risk of nine cancers
Authors: Smith-Byrne Karl , Hedman Åsa , Dimitriou Marios , Desai Trishna , Sokolov Alexandr V. , Schioth Helgi B. , Koprulu Mine , Pietzner Maik , Langenberg Claudia , Atkins Joshua , Cortez Ricardo , McKay James , Brennan Paul , Zhou Sirui , Richards Brent J. , Yarmolinsky James , Martin Richard M. , Borlido Joana , Mu Xinmeng J. , Butterworth Adam , Shen Xia , Wilson Jim , Assimes Themistocles L. , Hung Rayjean J. , Amos Christopher , Purdue Mark , Rothman Nathaniel , Chanock Stephen , Travis Ruth C. , Johansson Mattias , Mälarstig Anders
Published: May 2023

Background

Understanding the role of circulating proteins in cancer risk can reveal key biological pathways and identify novel therapeutic targets for cancer prevention.

Methods

We investigated the associations of 2,094 circulating proteins with risk of nine common cancers (bladder, breast, endometrium, head and neck, lung, ovary, pancreas, kidney, and malignant non-melanoma) usingcispQTL Mendelian randomisation (MR) and colocalization. Findings for proteins with support from both MR, after correction for multiple-testing, and colocalization were replicated using an independent cancer GWAS. Additionally, MR and colocalization phenome-wide association analyses (PHEWAS) were conducted to identify potential adverse side-effects of altering risk proteins. Finally, we mapped cancer risk proteins to drug and ongoing clinical trials targets.

Results

We identified 40 proteins associated with cancer risk, of which a majority replicated and were novel. Among these were proteins associated with common cancers, such as PLAUR and risk of breast cancer [odds ratio per standard deviation increment (OR): 2.27, 95% CI: 1.88 to 2.74], and with high-mortality cancers, such as CTRB1 and pancreatic cancer [OR: 0.79, 95% CI: 0.73 to 0.85]. PHEWAS highlighted multiple links between proteins and potential adverse effects of protein-altering interventions. Additionally, 18 proteins associated with cancer risk mapped to existing therapeutic interventions, while 15 were not currently known to be under clinical investigation, such as GAS1 and triple negative breast cancer [OR: 1.88, 95% CI: 1.42 to 2.47].

Conclusion

Our findings emphasize the importance of proteomics for improving our understanding of cancer aetiology. Additionally, we demonstrate the benefit of in-depth protein PHEWAS analyses on risk proteins to identify potential adverse side-effects of protein-altering interventions. Using these methods, we identify a subset of risk proteins as potential drug targets for the prevention and treatment of cancer as well as opportunities for drug repurposing.
A Proteome-wide, Multi-Omics Analysis Implicates Novel Protein Dysregulation in Post-Traumatic Stress Disorder
Authors: Wang Jiawei , Li Hongyu , Wilson Rashaun , Wang Weiwei , Lam TuKiet T. ,   Traumatic Stress Brain Research Group, Lewis David A. , Glausier Jill , Holtzheimer Paul E. , Friedman Matthew J. , Williams Kenneth R. , Picciotto Marina R. , Nairn Angus C. , Krystal John H. , Duman Ronald S. , Zhao Hongyu , Girgenti Matthew J.
Published: May 2023

Post-traumatic stress disorder (PTSD) is a common and disabling psychiatric disorder. Here we present findings from the first proteome-wide study of the postmortem PTSD brain. We performed tandem mass spectrometry on large cohort of donors (N = 66) in two prefrontal cortical areas and found differentially expressed proteins and co-expression modules disturbed in PTSD. Integrative analysis pointed tohsa-mir-589as a regulatory miRNA responsible for disruptions in neuronal protein networks for PTSD, including the GABA vesicular transporter, SLC32A1. In addition, we identified significant enrichment of risk genes for Alzheimer’s Disease (N= 94,403), major depression (N = 807,553), and schizophrenia (N = 35,802) within PTSD co-expression protein modules, suggesting shared molecular pathology. Our findings highlight the altered proteomic landscape of postmortem PTSD brain and provide a novel framework for future studies integrating proteomic profiling with transcriptomics in postmortem human brain tissue.
Characterizing spatiotemporal variation in transmission heterogeneity during the 2022 mpox outbreak in the USA
Authors: Love Jay , LaPrete Cormac R. , Sheets Theresa R. , Vega Yon George G. , Thomas Alun , Samore Matthew H. , Keegan Lindsay T. , Adler Frederick R. , Slayton Rachel B. , Spicknall Ian H. , Toth Damon J.A.
Published: May 2023

Understanding how transmission heterogeneity varies over the course of an enduring infectious disease outbreak improves understanding of observed disease dynamics and informs public health strategy. We quantified the spatiotemporal variation in transmission heterogeneity for the 2022 mpox outbreak in the US using the dispersion parameter of the offspring distribution,k. Our methods fit negative binomial distributions to transmission chain offspring distributions informed by a large mpox contact tracing dataset. We found that estimates of transmission heterogeneity varied across the outbreak, but overall estimated transmission heterogeneity was low. When testing our methods on simulated data, estimate accuracy depended on contact tracing data accuracy and completeness. Because the actual contact tracing data had high incompleteness, the values ofkestimated from the empirical data may therefore be artificially high. Through simulation, we explore a method to correct estimatedkfor data incompleteness and, further, explore baseline expectations for temporal dynamics ofk.
Measuring the strength of maternal, newborn and child health care implementation and its association with childhood mortality risk in three rural districts of Tanzania
Authors: Baynes Colin , Kanté Almamy Malick , Exavery Amon , Kassimu Tani , Sikustahili Gloria , Mushi Hildegalda , Ramsey Kate , Sherr Kenneth , Weiner Bryan , Phillips James F.
Published: May 2023

This observational cohort study explores the association between maternal, newborn and child health care implementation strength and child survival in rural Tanzania from 2011-2015. We used data from a 2011 service availability and readiness assessment that quantified primary health care facilities’ ability to implement maternal, newborn and child health services and a population-level household survey that measured the utilization of such services to develop domain-specific summary measures of the effective coverage of facility-based maternal, newborn and child health care. We reduced domain specific effective coverage scores into fewer, independent scales of implementation strength using principal components analysis, and integrated them into gradients of the collective implementation strength exerted by groups of facilities on villages they served using Bayesian mixed effects models. We linked these scales to longitudinal data on the survival of children that were born in the catchment areas of the surveyed health facilities during the assessment period and followed up until December 31, 2015. We fit survival time models to estimate the relationship between implementation strength and child mortality. Increases in the implementation strength gauged by our first scale, which represented general facility readiness and the provision of antenatal, postnatal, and early childhood preventive services, were associated with child mortality risks that were, on average, 0.62 times lower. Increases in implementation strength gauged by our second scale, which represented sick childcare service provision, were associated with child mortality risks that were, on average, 0.56 times lower. We detected no significant child mortality response to our third scale, which represented intrapartum care provision. The findings suggest that strong implementation of antenatal, postnatal, early childhood preventive services and sick child care can accelerate child mortality reduction and that routine data on service availability and readiness can be used to measure health systems strengthening and its impacts.
Nature-based solutions in Australia: a systematic quantitative literature review of terms, application and policy relevance
Authors: Zhu Dan , Fraser Lily , Kendal Dave , Zhang Yue , Flies Emily J
Published: May 2023

Nature-based Solutions (NbS) are emerging as an approach to sustainable environmental management and addressing environmental and social issues in ways that benefit human well-being and biodiversity. NbS have been applied to social-environmental challenges such as climate change and urbanization, but with diverse conceptualisations and applications that may impact their effectiveness and broader uptake. Much of the literature and implementation of NbS has emerged from Europe and though NbS use is rising in Australia, the context is unclear. This systematic quantitative literature review aims to understand Nature-based Solutions in an Australian context.

Here we explore the meaning and practical uses of NbS in Australia, through three research questions: In Australia, 1) what is meant by the term ‘nature-based solutions’? 2) what socio-ecological challenges do NbS aim to address and how? 3) are there gaps in NbS research and policy application that are hindering uptake of NbS approaches?

We show that in Australia, local governments are using NbS in urban planning to address the compounding challenges brought on by climate change in the human-environment interfaces. However, there is no consensus on NbS definitions and approaches, research is focussed on urban areas and problems, and NbS implementation follows a bottom-up, localised pattern without an integrated policy framework. Based on these findings, we provide recommendations for improving the implementation of NbS in Australia including: 1) a consistency of NbS definition and awareness of NbS approaches; 2) interdisciplinary and interdepartmental collaboration on NbS methods and effectiveness and; 3) an integrated policy framework supporting NbS nationwide.
txci-ATAC-seq, a massive-scale single-cell technique to profile chromatin accessibility
Authors: Zhang Hao , Mulqueen Ryan M. , Iannuzo Natalie , Farrera Dominique O. , Polverino Francesca , Galligan James J. , Ledford Julie G. , Adey Andrew C. , Cusanovich Darren A.
Published: May 2023

Measuring chromatin accessibility is a powerful method to identify cell types and states. Performed at single-cell resolution, this assay has generated catalogs of genome-wide DNA regulatory sites, whole-organism cell atlases, and dynamic chromatin reorganization through development. However, the limited throughput of current single-cell approaches poses a challenge for implementing proper study designs, population-scale profiling, and/or very deep profiling of complex samples. To this end, we developed a 10X-compatible combinatorial indexing ATAC sequencing (“txci-ATAC-seq”), which is a combinatorial indexing framework that initially indexes (“pre-indexes”) chromatin within nuclei with barcoded transposases followed by encapsulation and further barcoding using a commercialized droplet-based microfluidics platform (10X Genomics). Leveraging this molecular hashing strategy, we demonstrate that txci-ATAC-seq enables the indexing of up to 200,000 nuclei across multiple samples in a single emulsion reaction, representing a ∼22-fold increase in throughput compared to the standard workflow at the same collision rate. To improve the efficiency of this new technique, we further developed a faster version of the protocol (“Fast-txci-ATAC-seq”) that separates sample pre-processing from library generation and has the potential to profile up to 96 samples simultaneously. We initially benchmarked our assay by generating chromatin accessibility profiles for 230,018 cells from five native tissues across three experiments, including human cortex (28,513 cells), mouse brain (48,997 cells), human lung (15,799 cells), mouse lung (73,280 cells), and mouse liver (63,429 cells). We also applied our method to a club cell secretory protein knockout (CC16-/-) mouse model to examine the biological and technical limitations of the mouse line. By characterizing DNA regulatory landscapes in 76,498 wild-type and 77,638 CC16-/-murine lung nuclei, our investigations uncovered previously unappreciated residual genetic deviations from the reference strain that resulted from the method of gene targeting, which employed embryonic stem cells from the 129 strain. We found that these genetic remnants from the 129 strain led to profound cell-type-specific changes in chromatin accessibility in regulatory elements near a host of genes. Collectively, we defined single-cell chromatin signatures in 384,154 nuclei from 13 primary samples across different species, organs, biological replicates, and genetic backgrounds, establishing txci-ATAC-seq as a robust, high-quality, and highly multiplexable single-cell assay for large-scale chromatin studies.
Limits to selection on standing variation in an asexual population
Authors: Barton Nick , Sachdeva Himani
Published: May 2023

We consider how a population responds to directional selection on standing variation, with no new variation from recombination or mutation. Initially, there areNindividuals with trait valuesz1, …,zN; the fitness of individualiis proportional to. The initial values are drawn from a distributionψwith varianceV0; we give examples of the Laplace and Gaussian distributions. When selection is weak relative to drift, variance decreases exponentially at rate 1/N; since the increase in mean in any generation equals the variance, the expected net change is justNV0, which is the same as Robertson’s (1960) prediction for a sexual population. In contrast, when selection is strong relative to drift, the net change can be found by approximating the establishment of alleles by a branching process in which each allele competes independently with the population mean and the fittest allele to establish is certain to fix. Then, if the probability of survival to timeof an allele with valuezisP(z), with mean, the winning allele is the fittest ofsurvivors drawn from a distribution. WhenNis large, there is a scaling limit which depends on a single parameter; the expecte d ultimate change isfor a Gaussian distribution, andfor a Laplace distribution (where 𝒲is the product log function). This approach also reveals the variability of the process, and its dynamics; we show that in the strong selection regime, the expected genetic variance decreases as ∼t−3at large times. We discuss how these results may be related to selection on standing variation that is spread along a linear chromosome.