bluuebunny/crossref_metadata_2025 huggingface dataset:
A Transfusion Regimen With Same-donor Packed Red Blood Cells Reduces Exposure to Multiple Blood Donors in Craniosynostosis Surgery
Authors: Uslu Ahmed , Mogensen Stefan , Lubenow Norbert , Enblad Per , Nilsson Pelle , Nowinski Daniel , Frykholm Peter
Published: May 2024

In major craniosynostosis surgery with moderate to severe blood loss, patients may be exposed to multiple donors. We have previously reported a method for reducing donor exposure using mixed pediatric units including plasma. To further reduce donor exposure, we used plasma-free divided pediatric units. The study aimed to investigate the feasibility of the new strategy for reducing donor exposure. This prospective observational study recruited children younger than 1 year who were scheduled for nonsyndromic craniosynostosis surgery. One adult red blood cell unit was divided into 4 equal units on the day before the operation for use intra- or postoperatively. Number of donor exposures, estimated blood loss, crystalloid, colloid, and blood product volumes, and coagulation parameters were evaluated. Nineteen infants were included. The mean estimated blood loss was 19 (3) mL/kg and the transfusion volume was 17 (7) mL/kg. The median donor exposure per patient was 1 (range, 1–3). During surgery, all infants received at least one DPU. Two infants received transfusions from more than one donor during the intraoperative period. In the first 24 hours postoperatively, 14 infants received transfusion; 10 received only DPUs, whereas 4 received from multiple donors. In all, multiple donor exposure was prevented in 14 of 19 infants. Postoperative Pk-INR was 1.33 (0.16); no plasma or platelets were transfused. The plasma-free DPU transfusion protocol may be useful to reduce donor exposure in open craniosynostosis surgery in infants.
Comparison of the Effect of Platelet-rich Plasma (PRP) and Fat Graft on Autologous Bone Grafting in a Randomized-controlled Experimental Skull Model
Authors: Gunes Deniz , Oksuz Sinan , Koseoglu Resit Dogan , Gokce Erkan
Published: May 2024

Gold standard method for the treatment of critical-sized bone defects is the autogenous bone grafting procedure. A number of new and potentially useful adjuncts currently are being investigated to enhance the success of bone grafting. We propose to evaluate the effect of the most known and easily obtained 2 biological materials, fat graft and platelet-rich plasma (PRP), on bone graft healing. Twenty-seven New Zealand male rabbits were included in this randomized, controlled study. Two-sided 15-mm diameter bone defects were created in the parietal bones and the bones taken were replaced right-to-left and vice versa with 1 control group, 1 fat graft applied group, and the last one PRP applied group. Histologic evaluation and 3-dimensional maxillofacial computerized tomography were performed and bone density was calculated. In radiologic analysis, bone density was significantly different in the PRP group compared with the control and fat graft group in the 12th week (P<0.05). In histologic scoring analysis, the PRP group had a better score than the control and fat graft group, while the fat graft group was worse than the control group in the 6th week (P<0.05). The addition of PRP had a positive effect whereas fat graft had a negative effect on bone graft healing compared with the control group.
Endoscopic Resection of Nasal Septal Chondroma
Authors: Demir Murat , Bahadir Osman , Çobanoğlu Hatice Bengü
Published: May 2024

Chondromas are benign cartilaginous tumors and rarely develop in the nasal septum. Although it causes different symptoms depending on the location and size of the tumor, the most common complaints are nasal obstruction and epistaxis. A submucosal mass narrowing the nasal passage can be seen in the septum by an endoscope. Computed tomography gives information about the localization and size of the mass. A definitive diagnosis is made by histopathologic examination. Treatment is surgical excision. Endoscopic surgery provides a less invasive and successful treatment. This case series aims to share that 2 cases with a diagnosis of nasal septal chondroma were successfully treated with endoscopic surgery.
Could Cerebral Inflammatory Lesions be the Cellular Origin of Primary Central Nervous System Lymphoma?
Authors: Ma Jie , Zhang Jianning , Chen Tao , Bai Hongmin , Yu Xinguang , Wang Hongwei
Published: May 2024

Introduction:

Primary central nervous system lymphoma (PCNSL) presents a diagnostic enigma due to the inherent absence of lymphoid tissue in the central nervous system (CNS). The hypothesis posits that lymphocytes infiltrating the CNS during inflammatory responses could represent a cellular source for PCNSL, challenging traditional understandings of its etiology.

Patient concerns:

In 2 illustrative cases, patients presented with neurological symptoms initially misdiagnosed as encephalitis and demyelinating disease, respectively. These diagnoses were established based on clinical assessments and initial biopsy findings.

Diagnosis:

Subsequent biopsies, conducted months after the first signs of disease, confirmed the diagnosis of PCNSL in both patients. Identifying CD20-positive tumor cells was pivotal, indicating a B-cell lymphoma origin.

Interventions:

Treatment strategies included high-dose methotrexate chemotherapy for both patients. In addition, the second patient underwent adjuvant whole-brain radiotherapy after the chemotherapy regimen.

Outcomes:

The therapeutic approach significantly reduced tumor size in both cases, with no evidence of recurrence observed during the follow-up period. This outcome underscores the potential efficacy of the chosen interventions.

Conclusion:

In response to inflammatory lesions, lymphocyte infiltration into the CNS may serve as a pivotal origin for tumor cells in PCNSL. These cases highlight the complexity of diagnosing CNS disorders and suggest that various forms of encephalitis in the early stages could influence the prognosis of lymphoma. This insight into the cellular origins and treatment responses of PCNSL contributes to a broader understanding of its pathophysiology and management.
Esthetic Posterior Reconstruction of Lower Eyelid Using Stripe-Shaped Antihelix Cartilage With Perichondrium
Authors: Nakao Ko , Sakai Shigeki , Kazuo Kishi
Published: May 2024

Eyelid malignancies are often resected in the entire layer, typically requiring anterior and posterior lamellae reconstruction. Posterior lamella reconstruction has been reported using grafts from the nasal septum, palatal mucosa, and auricular cartilage, which have advantages and disadvantages. The authors performed anterior and posterior lamellar reconstruction using a local skin flap and stripe-shaped anti-helical cartilage with the perichondrium in 3 total defect cases after basal cell carcinoma resection of the lower eyelid. The auricular cartilage was excised in strips with the surrounding perichondrium attached and simultaneously reconstructed, with the auricular cartilage as the tarsal and the perichondrium as the conjunctival substitute. In all 3 cases, good results were obtained without eyelid ectropion or corneal irritation 1 year postoperatively. No auricular deformities were observed. However, partial lower eyelid ptosis was observed in 2 cases. In future cases, correctively over-fixating the lower eyelid morphology is necessary.
An Effective Technique for the Correction of Orbital Hypertelorism to Prevent Recurrence
Authors: Dong Guoxuan , Gu Tianyi , Zhang Chao , Teng Li
Published: May 2024

Objective:

To investigate the efficacy and safety of medial orbital wall osteotomy with medial displacement combined with lateral orbital wall Medpor artificial material implantation in the treatment of orbital hypertelorism.

Methods:

A retrospective analysis was performed on patients who underwent the above surgical procedures from 2010 to 2019, and long-term follow-up was conducted to record surgery-related complications and evaluate postoperative outcomes.

Results:

Four patients (3 males and 1 female) were followed up for 24 months. All patients were satisfied with the postoperative results. There was no diplopia, vision loss, eye movement disorder or other vision-related complications. There was no implant rejection, infection or exposure.

Conclusion:

This operation is a modification of the traditional surgical method of medial orbital wall osteotomy. It is safe and effective for the treatment of orbital hypertelorism.
Implant in the Area of Cemento-osseous Dysplasia: Secondary Infection After Osseointegration and Loading
Authors: Kim Jeseong , Yoo Seung Rim , Yeom Han Gyeol , Lim Hun Jun , Kim Bong Chul
Published: May 2024

This case report presents the clinical details of a 60-year-old woman who experienced a secondary infection 5 years postimplant placement and loading in a region affected by cemento-osseous dysplasia (COD). We conducted the simultaneous removal of the implant and the COD mass, which had become osseointegrated with the implant. Healing of the affected area was successful. Caution is paramount during implant placement in COD-affected areas, particularly during the intermediate and osteosclerotic stages, due to compromised vascularity.
Relation of Mandibular Canal Discontinuity and IAN Paresthesia in Operated Cases of Mandibular Fracture
Authors: Sahoo Nanda Kishore , Vashisht Sahil , Vaswani Himani , Pandey Swati
Published: May 2024

Introduction:

Mandibular fractures are common in maxillofacial trauma, often requiring surgical intervention for optimal recovery. One critical concern during such procedures is the potential for nerve damage, specifically involving the mandibular canal. This study aims to investigate whether the presence of postoperative mandibular canal discontinuity is associated with an increased risk of nerve damage.

Methodology:

A retrospective analysis was conducted on a cohort of 72 postoperative mandibular fracture patients. In total, 58 patients had entire mandibular canal continuity, while 14 showed discontinuity. Clinical records and follow-up data were examined to assess the occurrence of nerve injury. Statistical analysis was performed to determine the significance of any correlation.

Results:

Of the 14 patients with mandibular canal discontinuity, 9 (64.28%) exhibited paresthesia. In patients where mandibular canal continuity was maintained, 5 (8.62%) patients reported paresthesia. These results suggest a higher incidence of paresthesia in patients with mandibular canal discontinuity, albeit with a small sample size. Notably, only 3 patients in the discontinuity group did not show any sign of improvement, while the remaining patients in both groups demonstrated complete recovery in 6 months of follow-up period.

Discussion:

The findings suggest a potential link between mandibular canal discontinuity and an increased risk of paresthesia in postoperative mandibular fracture patients. It is hypothesized that discontinuity may lead to nerve compression, irritation, or direct damage during healing. The observed complete recovery in most patients, including those with paresthesia, highlights the potential for the nervous system to repair itself over a period of time. However, further studies with larger sample sizes are warranted to establish a more definitive correlation.

Conclusion:

This study provides preliminary evidence that mandibular canal discontinuity may contribute to a higher incidence of paresthesia in postoperative mandibular fracture patients. Clinicians should be cautious when addressing mandibular fractures to minimize the risk of nerve damage, particularly in cases involving canal discontinuity. The encouraging trend of complete recovery among the majority of patients suggests a positive prognosis for nerve healing.
Structural Rhinoplasty as an Effective Surgical Approach for Frontonasal Dysplasia
Authors: Chaisrisawadisuk Sarut , Chaisrisawadisuk Somboon
Published: May 2024

Frontonasal dysplasia (FND), a rare congenital craniofacial disorder, primarily influences the development of midline craniofacial structures. A notable manifestation of this condition is nasal hypoplasia. This report details the treatment of a 19-year-old male patient diagnosed with FND accompanied by a severe case of nasal hypoplasia. The authors used structural rhinoplasty to achieve total nasal reconstruction. Albeit with some minor sequelae, the outcome of this surgery was markedly positive, enhancing both the cosmetic appearance and functional capacity of the nose. This case underscores the effectiveness of structural rhinoplasty as a feasible therapeutic approach for individuals suffering from FND and its associated nasal hypoplasia.
A New Option to Preserve Esthetics in Perioral Defect Reconstruction With Normal Anatomical Structures: Bipedicled Preexpanded Forehead Flap With Random Skin Flap Extension
Authors: Yang Ruomeng , Jin Shengyang , Zang Mengqing , Zhu Shan , Li Shanshan , Han Tinglu , Liu Yuanbo
Published: May 2024

Plastic surgeons charged with reconstructing extensive perioral defects face dual challenges of functional restoration and esthetic considerations. While forehead flaps are commonly used to reconstruct perioral defects, in cases involving partial upper lip defects where normal anatomical structures are preserved, traditional forehead flaps may compromise esthetics. This study aimed to address this issue by employing bipedicled preexpanded forehead flaps based on the frontal branches of the superficial temporal artery (hereafter, “STA-bfb–based preexpanded forehead flap”) with random flap extensions to repair perioral defects. Between April 2004 and July 2020, 7 patients (5 males and 2 females; 6 had post-burn facial scars involving the entire lower lip and part of the upper lip, and 1 presented with noma sequelae) underwent perioral defect reconstruction using this approach. Tissue expanders were placed in the forehead donor area, and an STA-bfb–based preexpanded forehead flap with random flap extensions was used to repair the perioral defect. The flap pedicle was divided into 3 weeks. All flaps remained viable with no perfusion-related complications. At follow-up 12 to 96 months later, the color and texture of the flaps demonstrated excellent compatibility with the surrounding skin, suggesting that the use of an STA-bfb–based preexpanded forehead flap with random skin flap extensions is a reliable method for repairing perioral defects. The authors’ results have implications for plastic surgeons seeking a solution for challenging perioral defect reconstructions, balancing the need for esthetic outcomes with functional restoration.
Transconjunctival Levator Aponeurosis-Müller Muscle Complex Plication to Correct the Acquired Ptosis Following Double-Eyelid Surgery
Authors: Jeong Yeonwoo , Yoo Hyokyung , The Tran Vinh Vuong , Hong Ki Yong , Kim Sukwha
Published: May 2024

One of the most common adverse outcomes of an upper blepharoplasty involving double-eyelid surgery is asymmetric upper eyelids due to unbalanced supratarsal folds or a difference in the palpebral fissure height. This study aimed to evaluate the efficacy and safety of transconjunctival levator aponeurosis-Müller muscle complex plication for correcting acquired ptosis following double-eyelid surgery. This retrospective study evaluated 18 patients who underwent transconjunctival levator aponeurosis-Müller muscle complex plication between June 2016 and June 2019 to correct acquired ptosis. On the basis of the main area of eyelid drooping, ptosis was categorized as central (mid-pupillary), medial (medial limbus), or lateral (lateral limbus). Preoperative and postoperative palpebral fissure heights were measured and compared. Three months postsurgery, the mean difference in palpebral fissure height between bilateral eyes decreased from 0.96 to 0.04 mm in the medial (P<0.001), from 0.93 to 0.00 mm in central (P=0.003), and from 1.30 to −0.03 mm in lateral ptosis (P=0.079). In 13 patients who underwent unilateral correction, the amount of plication was significantly associated with increased palpebral fissure height at the medial limbus (P=0.043) and mid-pupillary line (P=0.035). All patients reported a significant improvement in satisfaction. Five patients experienced acute postoperative complications, including chemosis, conjunctival injection, and foreign body sensation, all of which were resolved after a month of observation. No asymmetries or recurrences were observed. Transconjunctival levator aponeurosis-Müller muscle complex plication is a minimally invasive, safe, and effective technique for correcting acquired ptosis following upper eyelid surgery.
Comprehensive 3-dimensional Positional and Morphological Analyses of Condyle and Glenoid Fossa in Patients with Skeletal Class II Malocclusion following Bimaxillary Orthognathic Surgery
Authors: Luo Si , Guo Songsong , Shi Yijin , Wang Hong , Zhang Ping , Jiang Hongbing , Cheng Jie
Published: May 2024

This study aimed to comprehensively and quantitatively characterize 3-dimensional (3D) positional and morphological changes of the condyle and glenoid fossa in patients with skeletal Class II malocclusion treated with bimaxillary orthognathic surgery. Twenty eligible patients treated at our institution from January 2016 to December 2021 with more than 12 months of postoperative follow-up were retrospectively enrolled. Radiographic data of cone-beam computed tomography (CBCT) for each patient were collected at 3 stages: 1 week preoperatively (T0), immediately after surgery (T1), and at least 12 months postoperatively (T2). Positional changes, surface and volumetric alterations of condyle, and bone remodeling in glenoid fossa were measured and compared based on voxel- and surface registrations in visual 3D methods. Most patients exhibited a tendency for condyles to shift posteriorly, laterally, superiorly, and rotated outward, downward, and forward immediately after surgery. Posterior, medial, superior movement and outward, upward, and backward rotation of condyles were observed during follow-up (T1-T2). Bone resorption frequently occurred in the posterior area of condylar surfaces, while bone remodeling was more common in the anterior region of the glenoid fossa. Reduced volume of the condyle was found in most cases, which was not associated with the amount of mandibular advancement. Overall, the condyle and its corresponding glenoid fossa remained relatively stable during the follow-up. Our results reveal positional and morphological alterations in the condyle and the glenoid fossa after bimaxillary orthognathic surgery in patients with skeletal class II malocclusion. These changes predominantly fall within the spectrum of physical adaption.
Complete Shrinking of Mixed Growth Hormone and Prolactin-Secreting Pituitary Adenoma With Bromocriptine Therapy Alone
Authors: Fan Jiayong , Shen Huimin , Mo Jun , Zhang Jianmin
Published: May 2024

A 40-year-old man presented with acromegaly, reduction of visual acuity and visual field, and elevated blood sugar. Imaging examinations demonstrated a large sellar adenoma with suprasellar extension that compresses the optic chiasma upward, spreads downward to the sphenoid sinus, and invades the cavernous sinus bilaterally. Random prolactin and growth hormone were beyond the scope of normal. The patient achieved complete shrinking of the adenoma by taking bromocriptine orally. For some kinds of giant mixed growth hormone-prolactin adenomas, surgical treatment is not necessary, and drug treatment can also achieve good results.
Combined Genioplasty and External Oblique Line Grafting: An Innovative Method to Improve Lower Facial Contour
Authors: Zang Tianying , Tang Xiaojun , Yin Lin
Published: May 2024

Background:

Microgenia and the accompanying plump cheeks or hamster-like facial contour are all unattractive appearances among the Asian. Genioplasty with autogenous bone grafting is one of the effective ways to improve microgenia, in which a suitable donor area with less additional damage, lower infection rate, and more excellent effect is crucial.

Methods:

Patients who had undergone genioplasty and autogenous external oblique line grafting (G-EOL) were followed up. The operation-related complications, preoperative, and long-term follow-up 3-dimensional spiral computed tomography (3D-CT) were collected and analyzed.

Results:

Eight female patients who had received G-EOL and received 1 to 3 years of follow-up were included in this study. There were no short-term or long-term complications. CT data of bone of 8 patients and CT data of soft tissue of 6 patients at the preoperative and long term were compared. Through comparing CT data, the width at the level of the intersection of EOL and mandibular body, and the protrusion of the bony chin had improved significantly; the P values were all <0.001. Through measuring the soft tissue and analyzing the data, the ratio of lower and middle facial width, and the distance from the lower lip to Ricketts’ line were all improved, with the P values 0.042 and 0.001, respectively.

Conclusions:

For patients with microgenia and hamster-like facial contour, the combination of genioplasty and autogenous external oblique line grafting is innovative and effective in improving both the front and side contour of the lower face simultaneously, with excellent stability, bone healing, and low complication rates.
Mandibular Osteomyelitis as the Earliest Clinical Manifestation of Maxillary Sinus Lymphoma
Authors: Liu Jian , Chi Jiang-peng , Zhu Xiang-kui , Sun Chao
Published: May 2024

Extranodal natural killer/T-cell lymphoma is a distinct subtype of non-Hodgkin lymphoma that originates from natural killer cells or cytotoxic T cells. Its diagnosis is challenging due to the rarity and lack of awareness, especially in cases where osteomyelitis of the jawbone is the initial symptom. This paper reports a case of extranodal natural killer/T-cell lymphoma presenting primarily with oral ulcers. Through analyzing the clinical and pathological characteristics, differential diagnosis, treatment and prognosis, and reasons for misdiagnosis of the disease, this study aims to provide references for clinical diagnosis and treatment.
Perineural Invasion is an Important Prognostic Factor in Patients With Radically Resected (R0) and Node-negative (pN0) Pancreatic Cancer
Authors: Schouten Thijs J. , Kroon Victor J. , Besselink Marc G. , Bosscha Koop , Busch Olivier R. , Crobach A. Stijn L.P. , van Dam Ronald M. , Doukas Michail , Fariña Sarasquesta Arantza , Festen Sebastiaan , Groot Koerkamp Bas , van der Harst Erwin , Heij Lara R. , de Hingh Ignace H.J.T. , Kazemier Geert , Liem Mike S.L. , de Meijer Vincent E. , Mieog J. Sven D. , Patijn Gijs A. , Raicu G. Mihaela , Roos Daphne , Schreinemakers Jennifer M.J. , Stommel Martijn W.J. , Wilmink Hanneke J. , Wit Fennie , Brosens Lodewijk A.A. , van Santvoort Hjalmar C. , Molenaar I. Quintus , Daamen Lois A. ,   for the Dutch Pancreatic Cancer Group
Published: May 2024

Objective:

To investigate the association between perineural invasion (PNI) and overall survival (OS) in a nationwide cohort of patients with resected pancreatic ductal adenocarcinoma (PDAC), stratified for margin negative (R0) or positive (R1) resection and absence or presence of lymph node metastasis (pN0 or pN1-N2, respectively).

Background:

Patients with R0 and pN0 resected PDAC have a relatively favorable prognosis. As PNI is associated with worse OS, this might be a useful factor to provide further prognostic information for patients counselling.

Methods:

A nationwide observational cohort study was performed including all patients who underwent PDAC resection in the Netherlands (2014-2019) with complete information on relevant pathological features (PNI, R status, and N status). OS was assessed using Kaplan-Meier curves, and Cox-proportional hazard analyses were performed to calculate hazard ratio’s (HR) with corresponding 95% confidence intervals (CI).

Results:

In total, 1630 patients were included with a median follow-up of 43 (interquartile range 33-58) months. PNI was independently associated with worse OS in both R0 patients (HR 1.49 [95%CI 1.18-1.88]; P<0.001) and R1 patients (HR 1.39 [95% CI 1.06-1.83]; P=0.02), as well as in pN0 patients (HR 1.75 [95%CI 1.27-2.41]; P<0.001) and pN1-N2 patients (HR 1.35 [95% CI 1.10-1.67]; P<0.01). In 315 patients with R0N0, multivariable analysis showed that PNI was the strongest predictor of OS (HR 2.24 [95% CI 1.52-3.30]; P<0.001).

Conclusion:

PNI is strongly associated with worse survival in patients with resected PDAC, in particular in patients with relatively favorable pathological features. These findings may aid patient stratification and counselling and help guide treatment strategies.
Impact of Obesity on Midurethral Sling Failure in a Highly Hispanic Population
Authors: Song Jun , Song Xuemei , Wang Zhu , Alas Alexandriah
Published: May 2024

Importance

Mixed data exist in the literature regarding the impact of obesity on midurethral sling (MUS) failure rates.

Objective

The aim of this study was to evaluate the impact of obesity and Hispanic ethnicity on MUS failure.

Study Design

This was a retrospective cohort study of females who underwent MUS surgery, alone or with concomitant prolapse repair, with at least 1 year of follow-up. Body mass index (BMI) classes were categorized as normal (<25 kg/m2), overweight (25–29.9 kg/m2), obese (30–39.9 kg/m2), and severe obesity (≥40 kg/m2). The primary outcome was MUS failure, defined as a composite of subjectively unchanged or worsened symptoms or need for additional procedures. Secondary outcomes included risk factors related to MUS failure and the effect of ethnicity on MUS failure rates.

Results

A total of 322 women were included for analysis. The mean age was 52.3 years. Increasing BMI was associated with higher MUS failure, with multivariate logistic regression showing a 5% increased risk for each 1 kg/m2 BMI increase. Failure rates were significantly different between normal BMI and severe obesity (16.7% vs 36.4%, P = 0.04). After adjusting for other variables, transobturator slings had a higher risk of failure compared with retropubic slings, whereas surgeon training and patient ethnicity did not affect failure rates.

Conclusions

We found that increasing BMI was associated with higher MUS failures, with significantly higher failure rates in the severely obese population. Although MUS remains the standard of care for treatment of SUI, based on our findings, counseling should be individualized to the patient, taking into account each patient’s unique characteristics.
Comparison of shelf-stable and conventional resuscitation products in a canine model of hemorrhagic shock
Authors: Edwards Thomas H. , Venn Emilee C. , Le Tuan D. , Grantham Lonnie E. , Hogen Talli , Ford Rebekah , Ewer Nicole , Gunville Ranger , Carroll Calli , Taylor Amy , Hoareau Guillaume L.
Published: May 2024

BACKGROUND

Treatment of severe hemorrhagic shock typically involves hemostatic resuscitation with blood products. However, logistical constraints often hamper the wide distribution of commonly used blood products like whole blood. Shelf-stable blood products and blood substitutes are poised to be able to effectively resuscitate individuals in hemorrhagic shock when more conventional blood products are not readily available.

METHODS

Purpose-bred adult dogs (n = 6) were anesthetized, instrumented, and subjected to hemorrhagic shock (mean arterial pressure <50 mm Hg or 40% blood volume loss). Then each dog was resuscitated with one of five resuscitation products: (1) lactated ringers solution and hetastarch (LRS/Heta), (2) canine chilled whole blood (CWB), (3) fresh frozen plasma (FFP) and packed red blood cells (pRBC), (4) canine freeze-dried plasma (FDP) and hemoglobin-based oxygen carrier (HBOC), or (5) HBOC/FDP and canine lyophilized platelets (LyoPLT). Each dog was allowed to recover after the hemorrhage resuscitation event and was then subjected to another hemorrhage event and resuscitated with a different product until each dog was resuscitated with each product.

RESULTS

At the time when animals were determined to be out of shock as defined by a shock index <1, mean arterial pressure (mmHg) values (mean ± standard error) were higher for FFP/pRBC (n = 5, 83.7 ± 4.5) and FDP/HBOC+LyoPLT (n = 4, 87.8 ± 2.1) as compared with WB (n = 4, 66.0 ± 13.1). A transient increase in creatinine was seen in dogs resuscitated with HBOC and FDP. Albumin and base excess increased in dogs resuscitated with HBOC and FDP products compared with LRS/heta and CWB (p < 0.01).

CONCLUSION

Combinations of shelf-stable blood products compared favorably to canine CWB for resolution of shock. Further research is needed to ascertain the reliability and efficacy of these shelf-stable combinations of products in other models of hemorrhage that include a component of tissue damage as well as naturally occurring trauma.
Myeloid cell networks determine reinstatement of original immune environments in recurrent ovarian cancer
Authors: Ghisoni Eleonora , Benedetti Fabrizio , Minasyan Aspram , Cunnea Paula , Grimm Alizée J. , Fahr Noémie , Desbuisson Mathieu , Capt Charlotte , Rayroux Nicolas , Gulhan Doga C. , Dagher Julien , Barras David , Morotti Matteo , Marín-Jiménez Juan A. , De Carlo Flavia , Chap Bovannak Stewen , Spagnol Giulia , Fleury Mapi , Fortis Katerina , Dorier Julien , Tissot Stephanie , Rusakiewicz Sylvie , Ferreira Humberto J. , Bassani-Stenberg Michal , Swisher Elizabeth M. , Kandalft Lana , Mastroyannis Spyridon A. , Montone Kathleen T. , Powell Daniel , Pittet Mikaël J. , Tanyi Janos L. , Coukos George , Fotopoulou Christina , Conejo-Garcia Jose R. , Laniti Denarda Dangaj
Published: May 2024

Immunotherapy has produced disappointing results in recurrent ovarian cancer (OC). However, the prognostic value of tumour-infiltrating lymphocytes (TILs) is largely based on the analysis of treatment-naive tumours. To understand the immunobiology of recurrent cancers, and their evolution, we profiled 170 patient-matched primary-recurrent OC samples from 69 patients of two independent cohorts. By capturing heterogeneous TIL distributions, we identified four immune phenotypes associated with differential prognosis, TILs states and TILs:myeloid networks, which dictate malignant evolution after chemotherapy and recurrence. Notably, recurrent tumours recapitulate the immunogenic patterns of original cancers. Mirroring inflamed human OC, preclinical recurrentBrca1muttumours maintained activated TILs:dendritic cells (DCs) niches and immunostimulatory tumour-associated macrophages (TAMs). Conversely, recurrentBrca1wttumours displayed loss of TILs:DCs niches and accumulated immunosuppressive myeloid networks featuringTrem2/ApoEhighTAMs andNduf4l2high/Galectin3highmalignant states. Our study highlights that persistent immunogenicity in recurrent OC is governed by the crosstalk between dissimilar myeloid cells and TILs, which is BRCA-dependent.
Follicular helper- and peripheral helper-like T cells drive autoimmune disease in human immune system mice
Authors: Khosravi-Maharlooei Mohsen , Vecchione Andrea , Danzl Nichole , Li Hao Wei , Nauman Grace , Madley Rachel , Waffarn Elizabeth , Winchester Robert , Ruiz Amanda , Ding Xiaolan , Fousteri Georgia , Sykes Megan
Published: May 2024

Human immune system (HIS) mice constructed in various ways are widely used for investigations of human immune responses to pathogens, transplants and immunotherapies. In HIS mice that generate T cellsde novofrom hematopoietic progenitors, T cell-dependent multisystem autoimmune disease occurs, most rapidly when the human T cells develop in the native NOD.Cg-PrkdcscidIl2rgtm1Wjl(NSG) mouse thymus, where negative selection is abnormal. Disease develops very late when human T cells develop in human fetal thymus grafts, where robust negative selection is observed. We demonstrate here that PD-1+CD4+peripheral (Tph) helper-like and follicular (Tfh) helper-like T cells developing in HIS mice can induce autoimmune disease. Tfh- like cells were more prominent in HIS mice with a mouse thymus, in which the highest levels of IgG were detected in plasma, compared to those with a human thymus. While circulating IgG and IgM antibodies were autoreactive to multiple mouse antigens, in vivo depletion of B cells and antibodies did not delay the development of autoimmune disease. Conversely, adoptive transfer of enriched Tfh- or Tph-like cells induced disease and autoimmunity-associated B cell phenotypes in recipient mice containing autologous human APCs without T cells. Tfh/Tph cells from mice with a human thymus expanded and induced disease more rapidly than those originating in a murine thymus, implicating HLA-restricted T cell-APC interactions in this process. Since Tfh, Tph, autoantibodies and lymphopenia-induced proliferation (LIP) have all been implicated in various forms of human autoimmune disease, the observations here provide a platform for the further dissection of human autoimmune disease mechanisms and therapies.
Contrasting patterns of spatial genetic structure in endangered southern damselfly (Coenagrion mercuriale) populations facing habitat fragmentation and urbanisation
Authors: Lévêque Agathe , Duputié Anne , Vignon Vincent , Duez Fabien , Godé Cécile , Vanappelghem Cédric , Arnaud Jean-François
Published: May 2024

Aim

Human-induced environmental changes result in habitat loss and fragmentation, impacting wildlife population genetic structure and evolution. Urbanised and geographically peripheral areas often represent unfavourable environments, reducing connectivity among populations and causing higher population genetic differentiation and lower intra-population genetic diversity. We examined how geographic peripherality and anthropogenic pressures affect genetic diversity and genetic differentiation in the protected southern damselfly (Coenagrion mercuriale, Odonata), which has low dispersal capabilities and specific habitat requirements and whose populations are declining.

Location

We studied two areas: one in semi-natural habitats at the periphery of the species geographic range (northern France) and the other more central to the species’ range, in an urbanised area surrounding the city of Strasbourg (Alsace, eastern France).

Methods

We genotyped 2743 individuals from 128 populations using eleven microsatellite loci. We analysed the spatial distribution of neutral genetic diversity (allelic richness, heterozygosity, levels of inbreeding, genetic relatedness), the extent of genetic differentiation, and population affiliations (sPCA analyses) within the two areas. We also examined fine-scale patterns of gene flow in the urbanised area of Alsace by investigating patterns of isolation by distance and estimating effective migration surfaces (EEMS method).

Results

Northern peripheral populations showed lower levels of genetic diversity and higher levels of genetic differentiation than central Alsacian populations. Although located in anthropised habitats, geographically central Alsacian populations showed high levels of gene flow, with dispersal events mainly occurring overland and not restricted to watercourses. However, the highly urbanised city of Strasbourg negatively impacted nearby populations by reducing levels of genetic diversity and increasing population genetic differentiation.

Main conclusions

These results showed the need for management action by restoring breeding sites and creating migratory corridors for peripheral southern damselfly populations. However, our results also highlighted the resilience of southern damselfly in central range populations facing strong urbanisation pressures.
Long-read sequencing reveals aberrant fragmentation patterns and origins of circulating DNA in cancer
Authors: Berman Benjamin P. , Erdman Sarah A. , Turatsinze Jean-Valery , Cayford Justin , Kelly Theresa K.
Published: May 2024

Circulating cell-free DNA (cfDNA), which includes tumor and immune-derived fragments, is often elevated in cancer patients relative to healthy individuals. This can be accompanied by changes in cfDNA fragmentation patterns, including fragment length distributions, fragment end sequences, and genomic context. Here, we survey fragmentation changes across 12 cancer types using Oxford Nanopore Technologies (ONT) shallow whole-genome sequencing. We confirm a hyperfragmentation pattern across a large fraction of the cancers and associate this with markers of altered DNase activity and elevation of circulating DNA and nucleosome levels. We also identify a cluster of cancers with fragments greater than 1 kilobase and distinguish these long fragments from genomic contamination based on length distribution and a DNASE1L3 fragmentation signature. Future studies using ONT sequencing will determine the prevalence and implications of this hypofragmentation phenotype across cancer.
Invasive adult jumping worms in Atlantic Canada are chill-susceptible
Authors: Adams Victoria E. , Chettiar Subash Raj , Clow Tanner M. , Gendron Emily , Gough Amber L. , Stewart Brianna E. M. , Cameron Erin K. , Toxopeus Jantina
Published: May 2024

The jumping wormAmynthas tokioensisis invasive in North America, and it has been expanding its range northward in recent years. Because low temperatures typically restrict the geographic distribution of organisms, our goal was to characterize the cold tolerance physiology of adult jumping worms from a site in New Brunswick, Canada (c. 45°N), with the intent of better understanding their geographic range limits. Most of our experiments supported the conclusion that these worms are chill-susceptible: they die during or after exposure to relatively mild low temperatures. When gradually cooled, adult worms lost neuromuscular coordination at approximately 0 °C and froze at a mean temperature of −4.5 °C. They did not survive freezing and showed poor survival following 1 h exposures to 0 °C and subzero temperatures. At higher mild temperatures (5 °C), the worms could survive short (up to 6 h) but not long (e.g., 48 h) chilling durations. We attempted to induce improved cold tolerance via a five-week gradual acclimation to fall-like temperatures, but fall-acclimated worms showed poor survival during and after this acclimation. Acclimation also did not induce accumulation of glucose, a typical cryoprotectant in earthworms. We suggest thatA. tokioensiscan likely persist wherever the growing season is sufficiently warm and long enough for the adults to mature, reproduce, and lay cocoons prior to the chilling temperatures associated with early fall. Future work examining the cold tolerance of the overwintering cocoons will be important for fully understanding the northern range limits of these jumping worms.
Hippocampal ripples predict motor learning during brief rest breaks in humans
Authors: Sjøgård Martin , Baxter Bryan , Mylonas Dimitrios , Thompson Megan , Kwok Kristi , Driscoll Bailey , Tolosa Anabella , Shi Wen , Stickgold Robert , Vangel Mark , Chu Catherine J , Manoach Dara S
Published: May 2024

Critical aspects of motor learning and memory happen offline, during both wake and sleep. When healthy young people learn a motor sequence task, most of their performance improvement happens not while typing, but offline, during interleaved rest breaks. In contrast, the performance of patients with dense amnesia due to hippocampal damage actually gets worse over the rest breaks and improves while typing. These findings indicate that an intact hippocampus is necessary for offline motor learning during wake, but do not specify its mechanism. Here, we studied epilepsy patients (n=17) undergoing direct intracranial EEG monitoring of the hippocampus as they learned the same motor sequence task. Like healthy young people, they showed greater speed gains across rest breaks than while typing. They also showed higher hippocampal ripple rates during these rest breaks that predicted offline gains in speed. This suggests that motor learning during brief rest breaks during wake is mediated by hippocampal ripples. These results expand our understanding of the role of hippocampal ripples beyond declarative memory to include enhancing motor procedural memory.
HiMoRNA and RNA-Chrom integration: Chromatin-Associated LncRNAs in Genome-Wide Epigenetic Regulation
Authors: Ilnitskiy Ivan S. , Ryabykh Grigory K. , Marakulina Daria A. , Mironov Andrey A. , Medvedeva Yulia A.
Published: May 2024

Long non-coding RNAs (lncRNAs) significantly contribute to genome structure and regulation. Many lncRNAs are known to interact with chromatin and in this way to affect gene expression patterns through epigenetic regulation. Still, experimental protocols for lncRNA-chromatin interactions do not provide any insight into the mechanisms of lncRNA-based genome-wide regulation. Here we present an integration of HiMoRNA – a resource containing correlated lncRNA-epigenetic changes in specific genomic locations genome-wide, – and RNA-Chrom, a resource featuring uniformly processed experimental data on RNA-chromatin interactions. Our integration approach allows generating interpretable and experimentally supported hypotheses on the mechanisms of lncRNA epigenetic regulation of gene expression. For this integration we have tailored the interface of HiMoRNA such that for many lncRNAs experimentally detected RNA-chromatin contacts are available from RNA-Chrom for browsing, analysis and downloading. HiMoRNA peaks supported by RNA-Chrom contacts can be explained by external experimental data. We believe that the integration of HiMoRNA and RNA-Chrom is a convenient and valuable approach that can provide experimental and mechanistic insights and greatly facilitate functional annotation of lncRNAs.
TNF signaling mediates cellular immune function and promotes malaria parasite killing in the mosquitoAnopheles gambiae
Authors: Samantsidis George-Rafael , Kwon Hyeogsun , Wendland Megan , Fonder Catherine , Smith Ryan C.
Published: May 2024

Tumor Necrosis Factor-α (TNF-α) is a proinflammatory cytokine and a master regulator of immune cell function in vertebrates. While previous studies have implicated TNF signaling in invertebrate immunity, the roles of TNF in mosquito innate immunity and vector competence have yet to be explored. Herein, we confirm the identification of a conserved TNF-α pathway inAnopheles gambiaeconsisting of the TNF-α ligand, Eiger, and its cognate receptors Wengen and Grindelwald. Through gene expression analysis, RNAi, andin vivoinjection of recombinant TNF-α, we provide direct evidence for the requirement of TNF signaling in regulating mosquito immune cell function by promoting granulocyte midgut attachment, increased granulocyte abundance, and oenocytoid rupture. Moreover, our data demonstrate that TNF signaling is an integral component of anti-Plasmodiumimmunity that limits malaria parasite survival. Together, our data support the existence of a highly conserved TNF signaling pathway in mosquitoes that mediates cellular immunity and influencesPlasmodiuminfection outcomes, offering potential new approaches to interfere with malaria transmission by targeting the mosquito host.
Device-free isolation of photoreceptor cells from patient iPSC-derived retinal organoids
Authors: Stone Nicholas E. , Bohrer Laura R. , Mullin Nathaniel K. , Cooke Jessica , Wright Allison T. , Stone Edwin M. , Mullins Robert F. , Tucker Budd A.
Published: May 2024

Autologous photoreceptor cell replacement therapy shows great promise for treating patients with multiple forms of inherited retinal degenerative blindness. Specifically, in disorders such as retinitis pigmentosa and Stargardt’s disease, selective death of photoreceptor cells results in irreversible blindness. Induced pluripotent stem cell (iPSC) derived retinal organoids, which faithfully recapitulate the structure of the neural retina, are an ideal source of photoreceptor cells required for these therapies. However, in addition to photoreceptor cells, retinal organoids also contain many other retinal cell types. Therefore, approaches for isolating fate committed photoreceptors from dissociated retinal organoids are desirable to produce photoreceptor cell replacement therapies. In this work, we present a partial dissociation strategy, which leverages the high level of organization found in retinal organoids to enable selective enrichment of photoreceptor cells without the use of specialized equipment or reagents such as antibody labels. Given that this technique can be performed with only standard plasticware and cGMP compliant reagents, it is an ideal candidate for use in the preparation of clinical cell therapies.
Multi-omics delineate growth factor network underlying exercise effects in an Alzheimer’s mouse model
Authors: Li Xin , Liu Chaozhong , Li Wenbo , Dai Yanwan , Gu Chaohao , Zhou Wenjun , Ciliberto Veronica C. , Liang Jing , S Udhaya Kumar. , Guan Dongyin , Hu Zhaoyong , Zheng Hui , Chen Hu , Liu Zhandong , Wan Ying-Wooi , Sun Zheng
Published: May 2024

Physical exercise represents a primary defense against age-related cognitive decline and neurodegenerative disorders like Alzheimer’s disease (AD). To impartially investigate the underlying mechanisms, we conducted single-nucleus transcriptomic and chromatin accessibility analyses (snRNA-seq and ATAC-seq) on the hippocampus of mice carrying AD-linked NL-G-F mutations in the amyloid precursor protein gene (APPNL-G-F) following prolonged voluntary wheel-running exercise. Our study reveals that exercise mitigates amyloid-induced changes in both transcriptomic expression and chromatin accessibility through cell type-specific transcriptional regulatory networks. These networks converge on the activation of growth factor signaling pathways, particularly the epidermal growth factor receptor (EGFR) and insulin signaling, correlating with an increased proportion of immature dentate granule cells and oligodendrocytes. Notably, the beneficial effects of exercise on neurocognitive functions can be blocked by pharmacological inhibition of EGFR and the downstream phosphoinositide 3-kinases (PI3K). Furthermore, exercise leads to elevated levels of heparin-binding EGF (HB-EGF) in the blood, and intranasal administration of HB-EGF enhances memory function in sedentary APPNL-G-Fmice. These findings offer a panoramic delineation of cell type-specific hippocampal transcriptional networks activated by exercise and suggest EGF-related growth factor signaling as a druggable contributor to exercise-induced memory enhancement, thereby suggesting therapeutic avenues for combatting AD-related cognitive decline.